What causes acute kidney injury? A complete guide to the main causes

An episode of acute kidney injury is rarely the result of one thing. In my practice I see a regular pattern: an elderly patient with stable chronic kidney disease, a recent viral illness, a few days of reduced fluid intake, a couple of contributing medications, and the kidneys give up. Working backwards to identify the cause is the most important step in treating it, and this article walks through how I approach that.

Acute kidney injury is not a single disease. It is a syndrome with many possible causes, and identifying the cause is the most important first step in treatment. The right treatment depends entirely on what is driving the injury. A patient who is dehydrated needs fluids. A patient with an obstructed urinary tract needs the obstruction relieved. A patient whose kidneys are reacting to a medication needs the medication stopped. Without finding the cause, treatment is at best a guess.

This guide walks through the main categories of AKI causes, with practical examples and what each implies for treatment and recovery.

The traditional classification divides AKI into three categories: pre-renal, intrinsic renal, and post-renal. The categories describe where the problem sits: before the kidney, in the kidney, or after the kidney. Each has a different mechanism, different investigations, and different treatments.

Pre-renal AKI is the most common category and accounts for around 60 to 70 per cent of all cases. The kidneys themselves are structurally intact, but their blood supply is reduced. With less blood reaching them, they cannot filter normally. The kidneys respond by reducing their filtration rate, which protects them from further damage in the short term but produces the picture of AKI.

The causes of pre-renal AKI are anything that reduces blood flow to the kidneys. Dehydration is the most common, often from vomiting and diarrhoea during a gastroenteritis. Severe infections that cause sepsis lower blood pressure throughout the body, including in the kidney circulation. Major bleeding has the same effect. Heart failure can reduce the effective volume reaching the kidneys even when total body water is not low. Excessive use of diuretics can over-dehydrate the patient. Liver disease with associated fluid shifts can cause a particular form called hepatorenal syndrome. Reduced fluid intake combined with heat or exertion can be a contributor in older adults.

Medications often interact with pre-renal causes. ACE inhibitors and angiotensin receptor blockers, which are essential medications for many patients with hypertension or kidney disease, dilate the blood vessels in the kidney to reduce pressure. During illness with dehydration, this dilation removes the kidney’s ability to compensate for reduced blood flow, and AKI develops. Non-steroidal anti-inflammatory drugs (such as ibuprofen, diclofenac, and naproxen) constrict the blood vessels that supply the glomeruli, again removing the kidney’s protective response. The combination of ACE inhibitor or ARB, diuretic, and NSAID during a viral illness is one of the most common triggers of community-acquired AKI in adults.

The treatment of pre-renal AKI focuses on restoring blood flow to the kidneys. Fluids are given, often intravenously in significant cases. The underlying cause is treated: the infection is addressed, the bleeding is stopped, the heart failure is optimised. Contributing medications are paused. Most pre-renal AKI resolves within days to a week once the cause is treated.

Intrinsic renal AKI accounts for around 20 to 30 per cent of cases. The damage is in the kidney tissue itself. The structures that do the work of filtration and reabsorption are injured, either by ischaemia (lack of blood supply, often the result of prolonged pre-renal injury), by toxic exposure, by inflammation, or by infiltration.

The most common form of intrinsic AKI is acute tubular necrosis. This is essentially what happens when pre-renal AKI is not treated quickly enough. The tubules of the kidney, which do the work of reabsorbing salts and water, are damaged by the prolonged lack of blood supply. They cannot work normally, and they take days to weeks to recover. Acute tubular necrosis is the most common form of AKI seen in hospital inpatients.

Interstitial nephritis is inflammation of the kidney tissue between the tubules. It is often a reaction to medications. The classical culprits are penicillins, cephalosporins, sulphonamides, and proton pump inhibitors (such as omeprazole). Some non-medication causes exist, including certain infections and autoimmune conditions. Interstitial nephritis can cause persistent kidney impairment if not recognised and treated, but most cases resolve once the offending medication is stopped.

Glomerulonephritis, inflammation of the kidney’s filtering units, can present as AKI in its more aggressive forms. ANCA-associated vasculitis and anti-GBM disease can cause rapidly progressive AKI over days to weeks, with a risk of permanent kidney damage if not treated urgently. These conditions are uncommon but important to recognise.

Vascular causes include atheroembolic disease (cholesterol crystals shed from arterial plaques during procedures), renal artery occlusion, and renal vein thrombosis.

Myoglobin from massive muscle injury (rhabdomyolysis) can damage the kidneys directly. This is seen after major trauma, prolonged immobility, severe exertion, and certain medication reactions.

Intrinsic AKI typically requires more intensive investigation than pre-renal AKI. A kidney biopsy may be needed in selected cases to establish the exact diagnosis. Treatment is directed at the cause: stopping the offending medication for interstitial nephritis, immunosuppression for vasculitis, supportive care for acute tubular necrosis.

Post-renal AKI accounts for around 5 to 10 per cent of cases. The kidneys are working normally, but the urine cannot drain out, and back-pressure damages function. Obstruction can occur at any level of the urinary tract: in the ureters, the bladder, or the urethra. Causes include kidney stones (particularly when stones obstruct both ureters or when there is a single kidney), bladder outlet obstruction from prostate enlargement, blood clots in the bladder, tumours of the bladder or pelvis, retroperitoneal fibrosis, and rarely external compression.

The distinctive feature of post-renal AKI is that imaging shows hydronephrosis (swelling of the kidneys’ drainage system from the back-pressure). A renal ultrasound is the standard initial investigation. Treatment is to relieve the obstruction, typically by inserting a urinary catheter for outlet obstruction or a ureteric stent or nephrostomy for ureteric obstruction. Most post-renal AKI resolves quickly once the obstruction is relieved.

Many AKI cases have more than one contributing cause. A typical scenario is an elderly patient with chronic kidney disease who develops a chest infection. The illness causes some dehydration. The infection lowers blood pressure. The ACE inhibitor they take for blood pressure becomes problematic in this setting. NSAIDs they take for joint pain compound the problem. Antibiotics may add a further insult. By the time the AKI is identified, three or four contributing factors are in play. Treating one without addressing the others is incomplete care.

For patients and their families, the practical messages are clear. AKI has a cause, and finding it matters. A clear history of the days before the AKI, including all medications taken (prescription, over-the-counter, and herbal), all illnesses, and any changes in fluid intake or urination, helps enormously. Reviewing all medications in the context of an AKI is routine and appropriate.

The recovery from AKI depends on the cause and the severity. Pre-renal and post-renal causes typically recover quickly. Intrinsic causes may take longer. Some intrinsic causes (such as severe interstitial nephritis or rapidly progressive glomerulonephritis) can leave permanent damage if not treated promptly. Follow-up at three to six months after a moderate or severe AKI is recommended to confirm recovery and check for any lasting consequences.

If you have had an episode of AKI, the most useful next steps are to ensure follow-up has been arranged, to review any medications that contributed, and to discuss any sick day guidance with your GP. Patients who have had AKI are at higher long-term risk of chronic kidney disease, future episodes of AKI, hypertension, and cardiovascular disease. Specialist follow-up reduces these risks.

I see private patients at Blackrock Clinic, The Beacon Hospital, Bon Secours Dublin, the Hermitage Medical Centre, and St Vincent’s Private Hospital. If you would like a consultation about your kidney health, you or your GP can contact my secretary through drrorymcquillan.ie. Most patients are seen within two to three weeks of referral.