Every acute kidney injury asks the same opening question: is the kidney under-perfused, structurally damaged, or blocked? The answer sets everything that follows. Two of the three categories reverse within hours if you act; the third needs you to name the injured compartment and the insult behind it. Approach AKI as a triage before a diagnosis, and you rarely miss the reversible cause hiding behind a frightening number.
The first fork: three ways a kidney's clearance fails
Filtration can fail for three structurally distinct reasons. The blood may not arrive with enough pressure or volume (pre-renal). The filtering tissue itself may be injured (intrinsic). Or the urine may have nowhere to go, so pressure backs up and cancels filtration (post-renal). Each maps to an anatomical level — before the kidney, within it, after it — and each carries a different first move. The discipline is to run all three hypotheses in parallel on first contact, not to anchor on the most familiar.
Sequence matters because reversibility is unevenly distributed. Pre-renal and post-renal injury, caught early, leave no scar; intrinsic injury often does. So the efficient clinician excludes the two reversible categories first — a bladder scan and a perfusion assessment cost minutes — and reserves the broader intrinsic work-up for what remains.
Pre-renal: the kidney that is starving, not broken
In pre-renal AKI the nephron is intact; it is simply not receiving enough perfusion to filter. The trigger is a fall in effective arterial blood volume — the volume the baroreceptors actually sense. That can mean true depletion (haemorrhage, vomiting, diarrhoea, over-diuresis) or a normal-to-high total volume that is mis-distributed, as in the venous congestion of heart failure, the splanchnic pooling of cirrhosis, or the vasodilation of sepsis. The kidney responds identically to both: it conserves salt and water and defends its filtration.
It defends GFR through autoregulation. Across a wide band of mean arterial pressures — roughly 80 mmHg and above in a previously normotensive person, higher in long-standing hypertension — the afferent arteriole dilates and the efferent constricts to hold glomerular pressure steady. Below that band, the compensation is exhausted and GFR falls with pressure. The practical message: a “normal” blood pressure does not guarantee adequate renal perfusion, and a patient can be maximally autoregulating right up to the moment they decompensate.
When the drugs break autoregulation
Autoregulation has two arms, and common drugs amputate each. Non-steroidal anti-inflammatories block the prostaglandins that dilate the afferent arteriole, so inflow falls. ACE inhibitors and ARBs block the angiotensin II that constricts the efferent arteriole, so glomerular pressure cannot be held. On their own, in a well-perfused patient, neither is dangerous. Combine them — and add a diuretic to lower volume — and you have the “triple whammy,” which removes both defences at once while reducing the volume they were defending. An elderly patient on this combination who then develops a diarrhoeal illness can lose substantial GFR in a day.
Post-renal: the plumbing problem
Obstruction lowers GFR mechanically. When urine cannot drain, pressure rises in the tubule and is transmitted backward to Bowman's space; as the pressure opposing filtration climbs, the net filtration pressure — and therefore GFR — falls. Early on there is no parenchymal damage at all, which is why prompt relief restores function completely. Leave it, and sustained back-pressure drives tubular atrophy and interstitial fibrosis that do not reverse.
For obstruction to cause significant AKI in a person with two kidneys, it must be bilateral or sit below the bladder — prostate, urethra — unless there is a single functioning kidney. The trap is output: partial or intermittent obstruction can leave urine output normal or even high, because the tubule loses its concentrating ability. Never reason that good output rules obstruction out. Anuria, by contrast, is obstruction (or a vascular catastrophe) until imaging says otherwise.
Intrinsic: naming the damaged compartment
Once perfusion and drainage are accounted for, intrinsic AKI is sorted by which compartment is injured. Tubular injury — acute tubular necrosis from ischaemia or toxins — is the commonest and shows muddy-brown granular casts. Interstitial injury — acute interstitial nephritis, usually drug-triggered — brings white cells, white-cell casts, and sometimes eosinophiluria, often with a rash or fever. Glomerular injury shows dysmorphic red cells and red-cell casts with proteinuria. Vascular injury spans large vessels (renal artery or vein) and small vessels (thrombotic microangiopathy, vasculitis, atheroembolism). The sediment is the fastest first sorter, and Chapter 3 takes it apart in detail.
The pre-renal to ATN continuum
Pre-renal azotaemia and ischaemic ATN are not separate diseases; they are the same insult at different durations. A briefly under-perfused kidney conserves and recovers — functional, reversible, tubules intact. Sustain the hypoperfusion and the tubular cells run out of oxygen: they lose their polarity, slough into the lumen, form obstructing casts, leak filtrate back across a denuded epithelium, and trigger tubuloglomerular feedback that further lowers GFR. Now the lesion is structural. Because the only reliable separator is whether function returns when perfusion is restored, the distinction is partly made in hindsight — which is precisely why early, adequate resuscitation matters: it decides which end of the spectrum the patient lands on.
After the relief: post-obstructive diuresis
Relieving a chronic obstruction is not the end of the story. Retained urea and salt create an osmotic drive, and tubules damaged by back-pressure cannot reabsorb normally, so a brisk diuresis can follow — occasionally litres. Most is appropriate offloading of accumulated volume, but a minority of patients become genuinely depleted and lose sodium, potassium, and magnesium fast. Watch the output and the electrolytes, replace a proportion of losses rather than chasing them litre-for-litre, and let the diuresis settle.
