Classify acute kidney injury. Describe acute tubular necrosis with its types, morphology and clinical course.

Definition and Classification

Distinguishing Pre-renal from Established Tubular Necrosis

Acute Tubular Necrosis

• The intact basement membrane in nephrotoxic injury is why recovery is better — surviving tubular cells can migrate along an intact scaffold and re-line the tubule
• Microscopy — tubular epithelial necrosis and sloughing, loss of the brush border, dilated tubules, casts of Tamm–Horsfall protein and cell debris, and interstitial oedema; glomeruli are normal

Clinical Course of Acute Tubular Necrosis

• The polyuric phase is dangerous in a different way — patients who survive the oliguric phase may die of dehydration and potassium loss if fluid and electrolytes are not replaced

Other Important Intrinsic Causes

• Acute interstitial nephritis — a hypersensitivity reaction, most often to drugs (penicillins, cephalosporins, NSAIDs, rifampicin, proton pump inhibitors, sulphonamides). The triad of fever, rash and eosinophilia with eosinophils in the urine; biopsy shows an interstitial infiltrate rich in eosinophils. Recovers on stopping the drug
• Renal cortical necrosis — extensive infarction of the cortex; follows obstetric catastrophe (abruptio placentae, septic abortion), severe shock and DIC. An important and often irreversible cause of renal failure in India
• Rhabdomyolysis — crush injury, prolonged immobility, seizures, statins; myoglobin is directly toxic and obstructs tubules; the urine is dark and dipstick-positive for blood with no red cells on microscopy

Consequences of Obstruction — Hydronephrosis

• Hydronephrosis is dilatation of the renal pelvis and calyces with progressive atrophy of the parenchyma, caused by obstruction to urine outflow
• Filtration continues for some time after obstruction, because filtrate is reabsorbed back across the tubules and into the lymphatics — which is why the pelvis dilates and the parenchyma is compressed rather than filtration simply stopping
• Naked eye — a progressively dilated, sac-like kidney with flattened papillae, blunted calyces and a thinned cortex; in extreme cases the kidney becomes a thin-walled bag of fluid
• Unilateral obstruction may be silent until the kidney is destroyed, because the other kidney compensates and creatinine stays normal — a common reason for late presentation
• Bilateral obstruction causes renal failure, and complete bilateral obstruction causes anuria
• Post-obstructive diuresis follows relief of chronic obstruction — a massive salt-losing diuresis requiring careful fluid and electrolyte replacement

Applied Aspects

• Always exclude obstruction first with an ultrasound — it is the least common cause but the most readily reversible, and missing it is unforgivable
• Correct volume depletion promptly; prolonged pre-renal failure becomes established tubular necrosis
• Stop nephrotoxic drugs — NSAIDs, ACE inhibitors, aminoglycosides and contrast; and adjust the dose of everything else that is renally excreted
• Hyperkalaemia is the immediate threat to life — treated with calcium gluconate to protect the myocardium, insulin with dextrose and salbutamol to shift potassium into cells, and dialysis for definitive removal
• Indications for urgent dialysis — refractory hyperkalaemia, severe acidosis, fluid overload with pulmonary oedema, uraemic pericarditis or encephalopathy, and certain poisonings
• In India, common precipitants include diarrhoeal dehydration, falciparum malaria, snake bite, obstetric haemorrhage and sepsis, and traditional or over-the-counter nephrotoxic remedies — most of them preventable
• Prognosis of acute tubular necrosis depends chiefly on the underlying illness, not on the kidney — mortality is high in multi-organ failure and low in isolated nephrotoxic injury
• Tubular cells regenerate, which is why recovery is possible at all; this depends on an intact basement membrane to migrate along
• Diuretics do not prevent or treat acute tubular necrosis — they may convert oliguric to non-oliguric failure, which simplifies fluid management but does not improve survival
• Contrast nephropathy is largely preventable by hydration, using the minimum volume of contrast, and avoiding it altogether in high-risk patients
• Careful fluid balance charting and daily weights are the most useful routine measures in an oliguric patient, and are often done badly
• Renal recovery may be incomplete, and a proportion of survivors are left with chronic kidney disease, so follow-up after apparent recovery is warranted
• Nephrotoxic drug dosing must be adjusted to the current function, not to a creatinine measured before the insult, which lags well behind the true filtration rate
• Snake bite causes acute kidney injury by several mechanisms at once — direct nephrotoxicity, haemolysis, rhabdomyolysis, DIC and hypotension — which is relevant across rural India
• Urine output is not a reliable marker on its own — non-oliguric acute kidney injury is common and is easily missed unless creatinine is checked
• Non-oliguric injury has a better prognosis than oliguric, reflecting less severe tubular damage rather than any benefit of the urine itself
• Hepatorenal syndrome is functional, not structural — the kidneys are histologically normal and work normally if transplanted, which is why treatment is directed at the liver and the splanchnic circulation