Acute Kidney Injury

Acute kidney injury is a sudden decline in renal function, occurring over hours to days, causing accumulation of nitrogenous waste products and disturbance of fluid, electrolyte, and acid base homeostasis. It is defined and staged using the KDIGO criteria, based on the rise in serum creatinine from baseline or the fall in urine output over a defined period.

Causes are classified anatomically into three categories, and this classification drives the initial diagnostic approach.

• Pre-renal injury results from reduced renal perfusion without intrinsic kidney damage, and is the most common category overall. Causes include hypovolemia (hemorrhage, dehydration, gastrointestinal losses), reduced effective circulating volume despite normal or increased total body fluid (heart failure, cirrhosis with ascites), sepsis and other causes of systemic vasodilation, and renal artery stenosis or other renal vascular compromise.

• Intrinsic renal injury reflects direct damage to the renal parenchyma itself. Acute tubular necrosis, most commonly from prolonged pre-renal insult or nephrotoxin exposure, is the most common intrinsic cause. Other intrinsic causes include glomerulonephritis (see Nephritic Syndrome entry), acute interstitial nephritis (frequently drug induced, classically from NSAIDs, penicillins, or proton pump inhibitors), and vascular causes such as vasculitis or thrombotic microangiopathy.

• Post-renal injury results from obstruction to urine outflow anywhere along the urinary tract, including benign prostatic hyperplasia, nephrolithiasis (particularly if bilateral or affecting a single functioning kidney), pelvic malignancy, and retroperitoneal fibrosis.

Presentation varies considerably depending on severity and underlying cause. Many cases are identified incidentally on routine bloods in an asymptomatic or minimally symptomatic patient, particularly in early or mild injury.

• More significant injury produces symptoms from uremia and fluid overload. Uremic symptoms include nausea, vomiting, anorexia, fatigue, pruritus, and, in severe or prolonged cases, confusion, asterixis, and pericarditis (uremic pericarditis, distinct from and generally more severe than the pericarditis discussed in that separate entry). Reduced urine output, ranging from oliguria to complete anuria, is common but not universal, since a proportion of patients maintain normal or even increased urine output despite significant renal impairment (non oliguric acute kidney injury).

• Fluid overload from impaired excretion causes peripheral edema, pulmonary edema with resulting dyspnea, and hypertension. Hyperkalemia, one of the most immediately dangerous complications, may be asymptomatic or may present with muscle weakness, palpitations, or, in severe cases, cardiac arrhythmia and arrest (see Electrolyte and Acid Base Disorders entry for the associated ECG changes).

Examination should specifically assess volume status, since this both guides the likely cause and directs immediate management: skin turgor, mucous membrane hydration, jugular venous pressure, and the presence or absence of peripheral or pulmonary edema all help distinguish a volume depleted, pre-renal picture from a volume overloaded, intrinsic or established injury picture. A palpable bladder or enlarged prostate on examination points toward a post-renal cause.

• Serum creatinine and urea, compared against any available baseline, confirm and stage the injury. Electrolytes, particularly potassium, must be checked urgently given the risk of life threatening hyperkalemia. A venous blood gas provides a rapid assessment of acid base status and can be obtained more quickly than a formal laboratory panel while decisions are made.

• Urinalysis is an essential and often underused test. Blood and protein suggest glomerulonephritis or another intrinsic process. Urinary eosinophils, though an insensitive and non-specific finding, can support a diagnosis of acute interstitial nephritis when clinically suspected. A bland urinalysis, without significant blood or protein, is more typical of pre-renal injury or established acute tubular necrosis.

• Renal tract ultrasound should be performed to look for hydronephrosis, which indicates a post-renal, obstructive cause requiring urgent decompression, and is generally recommended within 24 hours in any patient without an obvious alternative explanation for their injury, or sooner if obstruction is a strong clinical suspicion.

Further investigation is directed by the initial findings and clinical picture.

• Urinary sodium and fractional excretion of sodium can help distinguish pre-renal injury from established acute tubular necrosis in equivocal cases, though this is used less commonly in routine practice than urinalysis and clinical assessment.

• Autoimmune and vasculitis screening, including ANCA, complement levels, and anti-GBM antibody, is pursued where glomerulonephritis is suspected. A careful medication review is essential in every case, given how frequently drugs contribute to acute kidney injury through pre-renal, intrinsic, or, less commonly, post-renal mechanisms.

• Renal biopsy is reserved for cases where the cause remains unclear after non-invasive workup, particularly where an intrinsic glomerular or interstitial process is suspected and the result would change management.

Differentials essentially mirror the pre-renal, intrinsic, and post-renal categories above, and distinguishing between them is itself the central diagnostic task in acute kidney injury, rather than a separate step.

Immediate priorities focus on identifying and treating any immediately life threatening complication, then addressing the underlying cause.

Hyperkalemia with ECG changes or a potassium level high enough to pose immediate risk requires urgent treatment: intravenous calcium gluconate to stabilize the cardiac membrane, insulin with concurrent glucose to drive potassium intracellularly, nebulized salbutamol as an adjunct, and, where available, potassium binding agents, with dialysis considered for severe or refractory cases (see Indications for Dialysis entry).

Volume status should be corrected according to the underlying picture. Pre-renal injury from hypovolemia is treated with judicious intravenous fluid resuscitation, reassessing frequently to avoid overcorrection into fluid overload. Established fluid overload, by contrast, is managed with diuretics if the kidney retains some responsiveness, or fluid restriction, since further fluid administration in an overloaded, oliguric patient will worsen pulmonary edema without improving renal perfusion.

Nephrotoxic medications should be identified and stopped or dose adjusted wherever possible, including NSAIDs, certain antibiotics, and, where relevant, ACE inhibitors or ARBs, at least temporarily during the acute injury, with a plan to reintroduce once renal function has recovered if they remain clinically indicated. Contrast media should be avoided unless essential, given the additional nephrotoxic risk in an already injured kidney.

Post-renal obstruction requires urgent decompression, typically with catheterization for lower urinary tract obstruction, or nephrostomy or ureteric stenting for upper tract obstruction, and renal function often improves rapidly once obstruction is relieved.

Specific intrinsic causes are managed according to the underlying diagnosis: immunosuppression for glomerulonephritis or vasculitis (see Nephritic Syndrome entry), and withdrawal of the causative drug with corticosteroids considered in some cases of acute interstitial nephritis.

Dose adjustment of renally cleared medications is essential throughout the episode, and medication reconciliation should be repeated as renal function changes.

Renal replacement therapy is indicated for severe, refractory complications not responding to medical management (see Indications for Dialysis entry for the specific criteria).

Referral: nephrology for any severe, rapidly progressive, or unexplained acute kidney injury, for suspected intrinsic glomerular or interstitial disease requiring biopsy, or where renal replacement therapy is being considered; urology for post-renal obstruction requiring urgent decompression.