Acute kidney injury (AKI) refers to a clinical syndrome characterized by the rapid deterioration of renal function over a short period of time due to various causes. This results in a decrease in glomerular filtration rate (GFR), as well as the retention of creatinine, blood urea nitrogen, and disturbances in water, electrolyte, and acid-base balance, with severe cases leading to multisystem complications. AKI is a common and critical condition affecting multiple medical specialties, with an incidence of approximately 10–15% among hospitalized patients and as high as 50% in intensive care units. Studies indicate that about 10% of AKI patients require renal replacement therapy, and the mortality rate associated with AKI in hospitalized patients is approximately 23%. Furthermore, survivors of AKI have a significantly increased long-term risk of developing chronic kidney disease (CKD) and end-stage renal disease (ESRD).
Etiology and Classification
The numerous causes of AKI are classified into three main categories based on the anatomical site of onset: prerenal, renal (intrinsic), and postrenal.
Prerenal AKI
This type of AKI results from reduced blood perfusion to the renal parenchyma, leading to decreased GFR, and accounts for about 55% of AKI cases.
Renal AKI
This form is caused by injury to the renal parenchyma, including ischemic injury or damage induced by nephrotoxic drugs or toxins. Conditions such as acute tubular necrosis (ATN), acute interstitial nephritis (AIN), glomerular diseases, and renal vascular diseases fall under this category, representing approximately 40% of AKI cases, with ATN being the most common.
Postrenal AKI
This form arises from acute urinary obstruction, which can occur at any point in the urinary tract from the renal pelvis to the urethra, accounting for about 5% of AKI cases.
Pathogenesis and Pathophysiology
Prerenal AKI
Prerenal AKI occurs due to inadequate renal blood perfusion, which may result from reduced extracellular fluid volume, decreased effective circulating volume despite normal extracellular volume, or decreased glomerular capillary perfusion pressure caused by certain medications, including those that induce afferent arteriolar constriction or efferent arteriolar dilation.
Common causes include:
- Insufficient effective blood volume, such as in cases of significant hemorrhage, gastrointestinal fluid losses, renal fluid losses, losses through skin and mucosa, or fluid shifts into the extracellular space.
- Decreased cardiac output, which may occur with cardiac diseases, pulmonary hypertension, pulmonary embolism, or positive pressure mechanical ventilation.
- Systemic vasodilation caused by factors such as medications, sepsis, decompensated cirrhosis, or anaphylaxis.
- Renal artery vasoconstriction induced by drugs, hypercalcemia, or sepsis.
- Impaired renal autoregulation of blood flow, often caused by medications such as angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), non-steroidal anti-inflammatory drugs (NSAIDs), cyclosporine, and tacrolimus.
In the early stages of prerenal AKI, renal autoregulatory mechanisms help maintain relatively stable GFR and renal blood flow by adjusting the vascular tone of the afferent and efferent arterioles. However, if timely intervention does not occur, further ischemia to the renal parenchyma can lead to tubular cell injury and progression to renal AKI. The progression from renal perfusion insufficiency to ischemic renal injury is a continuum, with prognosis depending on the severity and duration of the initiating cause as well as the recurrence of subsequent renal insults.
Renal AKI
Renal AKI has various etiologies that can affect any part of the nephron or renal interstitium. Among these, ischemic and nephrotoxic injury to tubular epithelial cells is the most common mechanism, typically referred to as ATN. Other causes include AIN, glomerular diseases, renal vascular diseases, and renal transplant rejection.
ATN may be caused by ischemia or nephrotoxic drugs, often occurring as a result of multifactorial interactions, such as advanced age or concurrent diabetes. Although the initiating and ongoing mechanisms of ATN vary across different etiologies and pathological damage types, both reduced GFR and tubular epithelial cell injury play central roles.
Ischemic ATN progression from prerenal AKI typically involves four stages: initiation, extension, maintenance, and recovery.
Initiation Stage (lasting hours to days)
During this stage, reduced renal blood flow causes a decline in glomerular filtration pressure. Tubular epithelial cell death and detachment lead to the formation of casts, which obstruct the tubules, in addition to back-leak of filtrate into the interstitium. These factors collectively contribute to the reduction in GFR. Ischemic injury is most pronounced in the S3 segment of the proximal tubules and in the medullary portion of the thick ascending limb of the loop of Henle. If renal blood flow is not restored promptly, further cellular damage can result in apoptosis and necrosis.
Extension Stage (lasting days to weeks)
There is significant congestion in renal microvasculature, accompanied by ongoing tissue hypoxia and inflammatory responses. The junction of the cortex and medulla is the area most severely affected. GFR continues to decline progressively.
Maintenance Stage
The maintenance stage typically lasts 1 to 2 weeks and is characterized by persistently low GFR levels (often 5–10 ml/min). Urine output is often reduced, and complications of uremia may arise. During this time, renal tubular cells undergo continuous repair, migration, and proliferation to restore cellular and tubular integrity. While systemic hemodynamic conditions may improve, GFR usually remains low.
Recovery Stage
The recovery stage lasts from a few days to several months. Renal tubular epithelial cells gradually undergo repair and regeneration, leading to the gradual recovery of cellular and organ function. GFR begins to improve during this phase. If the recovery of tubular epithelial cell function is delayed, the reabsorption capabilities for solutes and water may lag behind the restoration of glomerular filtration, potentially leading to notable polyuria and electrolyte imbalances, such as early hyperkalemia and later hypokalemia.
Nephrotoxic acute tubular necrosis is caused by a variety of nephrotoxic substances, both exogenous and endogenous. Its mechanisms include direct tubular damage, renal vascular constriction, and tubular obstruction. Among exogenous nephrotoxic substances, medications are the most common, particularly aminoglycoside antibiotics and platinum-based antineoplastic agents, followed by heavy metals, chemical toxins, biological toxins (e.g., certain mushrooms or fish gallbladders), and microbial infections. Endogenous nephrotoxic substances include myoglobin, hemoglobin, light-chain proteins in multiple myeloma, uric acid salts, calcium, and oxalates.
Acute interstitial nephritis (AIN) is an important cause of renal AKI and can be classified into four major categories:
- Drug-induced AIN: This is commonly caused by non-steroidal anti-inflammatory drugs (NSAIDs), penicillins, cephalosporins, sulfonamides, warfarin, and others. The primary mechanism involves a type IV hypersensitivity reaction.
- Infectious AIN: This is seen primarily in bacterial or viral infections.
- Systemic diseases: These include systemic lupus erythematosus, Sjögren’s syndrome, cryoglobulinemia, and primary biliary cirrhosis.
- Idiopathic AIN: The cause remains unknown.
Renal vascular diseases leading to renal AKI include microvascular and macrovascular conditions. Microvascular conditions, such as thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), and HELLP syndrome (Hemolysis, Elevated Liver Enzymes, Low Platelet count), can result in glomerular capillary thrombosis and microvascular occlusion, ultimately causing AKI. Macrovascular conditions, such as atherosclerotic plaque rupture and embolization leading to renal microembolism and cholesterol embolism, or aortic dissection involving the renal arteries or renal artery dissection, may compromise renal blood flow and result in AKI.
Glomerular diseases causing renal AKI often involve primary and secondary crescentic glomerulonephritis, as well as acute exacerbations of lupus nephritis and IgA nephropathy.
Postrenal AKI
Postrenal AKI primarily occurs in patients with urinary tract obstruction. Functional obstruction may involve conditions such as neurogenic bladder. Organic urinary tract obstruction can result from intraluminal causes, such as bilateral kidney stones, renal papillary necrosis, blood clots, or bladder cancer, or extraluminal causes, such as retroperitoneal fibrosis, colorectal cancer, or lymphoma. Additionally, intratubular obstruction can result from the crystallization of substances such as uric acid salts, oxalates, acyclovir, sulfonamides, methotrexate, or light-chain proteins in multiple myeloma, as well as from the accumulation of cellular or proteinaceous casts within the tubules.
Pathology
Pathological changes in AKI vary significantly depending on the etiology and severity of injury. Macroscopically, kidneys may appear enlarged and soft, with the medulla exhibiting dark red discoloration and the cortex swollen and pale due to ischemia.
In ischemic ATN, histological findings in light microscopy include patchy and focal necrosis of tubular epithelial cells, detachment from the basement membrane, and intraluminal cast formation obstructing the tubular lumen. The S3 segment of the proximal tubule exhibits the most severe necrosis, followed by the medullary portion of the thick ascending limb of the loop of Henle. If the basement membrane remains intact, tubular epithelial cells can rapidly regenerate. Conversely, if the basement membrane integrity is lost, complete regeneration of the tubular epithelium may not occur.
In nephrotoxic ATN, morphological changes are most pronounced in the convoluted and straight portions of the proximal tubules. Tubular cell necrosis tends to be less severe than in ischemic ATN.
The pathological hallmark of AIN is interstitial inflammatory cell infiltration. Eosinophil infiltration is a key pathological feature in drug-induced AIN.
Clinical Manifestations
The clinical manifestations of AKI vary widely and depend on the underlying etiology and the stage of disease progression. Significant symptoms often appear only when renal function is severely impaired. Common symptoms include fatigue, loss of appetite, nausea, emesis, and reduced urine output. Volume overload can lead to acute left heart failure.
AKI is often initially diagnosed based on laboratory abnormalities, particularly absolute or relative increases in serum creatinine (Scr), rather than on clinical symptoms or physical signs.
The Clinical Course of Renal AKI Using ATN as an Example
Initiation Phase
During the initiation phase, patients are typically exposed to known or unknown triggers of ATN, such as hypotension, ischemia, sepsis, or nephrotoxic medications. At this stage, significant renal parenchymal injury has not yet occurred. If appropriate interventions are implemented during this phase, AKI can often be reversed. However, as tubular epithelial cell injury progresses, GFR declines gradually, transitioning the patient into the progression phase.
Progression and Maintenance Phases
These phases often last 7–14 days but can range from a few days to 4–6 weeks. GFR continuously declines during this period. Some patients develop oliguria (urinary output < 400 ml/day) or anuria (< 100 ml/day), while others maintain a urinary output greater than 400 ml/day, referred to as non-oliguric AKI. Irrespective of urine volume, as renal function deteriorates, patients may present with a spectrum of uremic symptoms primarily caused by the retention of uremic toxins, water, electrolyte imbalances, and acid-base disturbances.
Clinical manifestations of AKI during this phase include:
- Digestive system symptoms: Loss of appetite, nausea, emesis, abdominal distension, and diarrhea, with gastrointestinal bleeding occurring in severe cases.
- Respiratory symptoms: Pulmonary edema and infection caused by fluid overload.
- Cardiovascular symptoms: Hypertension and heart failure induced by oliguria and sodium-water retention, along with arrhythmias and myocardial changes due to toxin accumulation, electrolyte imbalances, anemia, and metabolic acidosis.
- Neurological involvement: Symptoms such as altered consciousness, restlessness, delirium, seizures, and coma, indicative of uremic encephalopathy.
- Hematological symptoms: A tendency to bleed or anemia.
Infections are common and severe complications of AKI. Additionally, during or as a result of disease progression, AKI can lead to multi-organ dysfunction syndrome, which carries a very high mortality rate. Water, electrolyte, and acid-base disorders in this phase frequently include fluid overload, metabolic acidosis, hyperkalemia, hyponatremia, hypocalcemia, and hyperphosphatemia.
Recovery Phase
During the recovery phase, GFR gradually improves and returns to normal or near-normal levels. Patients with oliguric AKI begin to experience increased urine output, followed by polyuria, and eventually return to normal urine volume. However, tubular epithelial cell function recovery typically lags behind GFR recovery and may take several months. A proportion of patients may end up with varying degrees of residual structural and functional kidney damage.
Laboratory and Auxiliary Examinations
Blood Tests
Results may reveal anemia, often mild in early stages; however, if renal function fails to recover over time, anemia can become more severe. Some underlying conditions that cause AKI, such as significant hemorrhage or severe infection, may also independently contribute to anemia. Serum creatinine (Scr) and blood urea nitrogen (BUN) levels progressively increase, with a faster rise observed in patients with high catabolic activity. Creatinine levels increase even more rapidly in cases of rhabdomyolysis. Serum potassium concentration tends to rise, while blood pH and bicarbonate concentrations decrease; hypocalcemia and hyperphosphatemia are also common.
Urine Tests
Urinary abnormalities in AKI vary significantly depending on the etiology:
Prerenal AKI
Proteinuria and hematuria are absent, though a small number of hyaline casts may be seen.
ATN
Small amounts of proteinuria, predominantly small-molecular-weight proteins, may occur. Urine sediment examination often reveals renal tubular epithelial cells, epithelial cell casts, granular casts, and a small number of red and white blood cells. Reduced tubular reabsorption function is indicated by fixed low specific gravity (usually < 1.015), urine osmolality < 350 mOsm/kg H2O, a urine-to-plasma osmolality ratio < 1.1, increased urinary sodium concentration, and a fractional excretion of sodium (FENa) > 1%. FENa is calculated as follows:
FENa = (Urinary sodium / Plasma sodium) ÷ (Urinary creatinine / Plasma creatinine) × 100%.
Note that urine tests should be performed prior to the administration of intravenous fluids or diuretics, as these can affect results.
Acute Interstitial Nephritis
A small amount of proteinuria, predominantly small-molecular-weight proteins, is common. Hematuria tends to be mild and features non-dysmorphic red blood cells. Mild leukocyturia may occur, and eosinophiluria may be observed in drug-induced cases; when eosinophils constitute > 5% of total white blood cells in urine, this finding is termed eosinophiluria. Marked tubular dysfunction is also common, with FENa > 1%.
Glomerular Disease
This condition often leads to significant proteinuria or hematuria, with dysmorphic red blood cells predominating. FENa is typically < 1%.
Postrenal AKI
Urine abnormalities are usually mild, with low levels of proteinuria and hematuria. Infection may introduce white blood cells in the urine. FENa is generally < 1%.
Imaging Studies
Ultrasound of the urinary tract is helpful for ruling out obstruction and distinguishing between AKI and CKD. In cases with a strong clinical suspicion of obstruction, retrograde or intravenous pyelography may be performed. CT angiography, MRI, or radionuclide imaging can assist in identifying vascular abnormalities, while definitive diagnosis often requires renal angiography. However, the use of contrast agents for imaging carries a risk of exacerbating kidney injury.
Renal Biopsy
Renal biopsy is a critical tool for differentiating the causes of AKI. If prerenal and postrenal causes are excluded and intrinsic AKI remains suspected without an identifiable cause, renal biopsy may be considered for definitive diagnosis.
Diagnosis
The diagnosis of AKI is generally not difficult when acute and progressive declines in glomerular filtration function are observed in combination with relevant clinical manifestations, laboratory findings, and imaging studies. According to the international clinical practice guidelines for AKI, the condition can be diagnosed when any of the following criteria are met:
- An increase in serum creatinine (Scr) of ≥0.3 mg/dl (≥26.5 μmol/L) within 48 hours.
- An increase in Scr to ≥50% of baseline within 7 days.
- A reduction in urine output to <0.5 ml/(kg·h) for at least 6 hours.
Table 1 Staging criteria for acute kidney injury (2012 KDIGO Guidelines)
Note: KDIGO refers to the Kidney Disease: Improving Global Outcomes organization.
It is important to note that when changes in urine output are used as the sole diagnostic and staging criterion, other factors affecting urine output, such as urinary tract obstruction, blood volume status, and diuretic use, should be taken into account. Additionally, because Scr is influenced by numerous factors and has limited sensitivity, it is not considered the optimal biomarker for detecting kidney injury. Emerging biomarkers, such as cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and insulin-like growth factor-binding protein 7 (IGFBP-7), may enhance the early diagnosis of AKI and the prediction of its prognosis and warrant further research.
Differential Diagnosis
A detailed medical history and physical examination are essential for identifying potential causes of AKI. The diagnostic process and differential diagnosis involve the following steps:
- Determining whether kidney injury is present and assessing its severity.
- Identifying the presence of severe complications requiring urgent intervention.
- Estimating the timeline of kidney injury onset to distinguish acute AKI from chronic kidney disease (CKD) or acute worsening of CKD.
- Identifying the underlying cause of AKI.
Evaluation typically includes screening for prerenal and postrenal causes, followed by assessment of potential intrarenal causes. If intrarenal AKI is identified, it should be determined whether it involves tubular-interstitial damage, glomerular disease, or vascular abnormalities. A systematic approach to investigating prerenal, intrarenal, and postrenal causes facilitates accurate early diagnosis and timely treatment.
Determining the Presence of Kidney Injury
Monitoring urine output and Scr levels in patients with high-risk factors for AKI is essential for timely detection. For patients with no prior history of CKD and no baseline Scr values available, the baseline Scr level may be estimated retrospectively using the MDRD formula.
Identifying Severe Complications Requiring Urgent Treatment
Kidney dysfunction may lead to life-threatening internal environment disturbances, with cases of sudden death in severe scenarios. These complications need to be promptly identified. Certain patients may have subtle clinical manifestations; hence, basic initial evaluations, including heart and lung auscultation, electrocardiography, and serum biochemistry, are necessary. Rapid assessment for immediate intervention is vital in cases such as severe hyperkalemia or metabolic acidosis.
Assessing the Timeline of Kidney Injury Onset
It is crucial to distinguish whether the decline in kidney function is acute or chronic, as CKD at any stage can worsen acutely due to various causes. This differentiation relies on a detailed medical history, physical examination findings, and laboratory and imaging investigations. AKI is often suggested by clinical clues, including potential precipitating factors such as conditions leading to reduced effective blood volume (e.g., orthostatic hypotension or hypotension), exposure to nephrotoxic drugs or substances, or urinary obstruction. Rapidly progressive clinical signs may include a pronounced decrease in urine output, gastrointestinal symptoms, or a substantial rise in Scr levels over a short period. Findings that support reduced blood volume as the etiology may include dry skin, reduced skin elasticity, tachycardia, hypotension, or narrow pulse pressure. Rash may suggest a drug-induced cause. Symptoms of water and sodium retention, including edema and pulmonary rales, may occur with reduced urine output. Imaging may show normal or enlarged kidneys, and laboratory findings (e.g., absence of anemia or secondary hyperparathyroidism, and normal calcium-phosphorus metabolism) help distinguish AKI from CKD.
Identifying the Underlying Cause of AKI
Using ATN (Acute Tubular Necrosis) as an example, the differential diagnosis includes the following:
Differentiation from Prerenal AKI
Prerenal AKI caused by renal hypoperfusion is the most common etiology. Medical history should explore triggers of absolute or relative volume depletion and recent use of medications such as NSAIDs, ACE inhibitors, or angiotensin II receptor blockers. Physical examination should note signs of volume depletion, including tachycardia, dry mucous membranes, poor skin turgor, and orthostatic hypotension. Laboratory findings may show a blood urea nitrogen (BUN) to Scr ratio >20:1 (after ruling out factors such as gastrointestinal bleeding or low muscle mass), unremarkable urine sediment, concentrated urine with reduced urinary sodium, fractional excretion of sodium (FENa) <1%, and a renal failure index (RFI) <1. RFI is calculated as follows:
RFI = Urinary sodium ÷ (Urinary creatinine/Serum creatinine)
Cases with suspected prerenal AKI may undergo tests such as a passive leg raise (PLR) maneuver or fluid challenge. PLR involves shifting the patient from a semi-recumbent position (45 degrees) to a supine position with legs raised 45 degrees for 1 minute, which increases return venous volume (approximately 250–450 ml). An increase in stroke volume >10% after PLR suggests volume responsiveness. If urine output improves following fluid therapy, prerenal AKI is implicated. Persistent oliguria after volume expansion, particularly in elderly patients with prolonged hypotension or heart failure, suggests progression to ATN.
Table 2 Diagnostic urine parameters in acute kidney injury
Differentiation from Postrenal AKI
A history of urinary stones, pelvic tumor, or previous surgeries, along with acute anuria, intermittent anuria, or renal colic, warrants consideration of postrenal AKI. Bladder catheterization may have both diagnostic and therapeutic significance. Imaging modalities such as ultrasound can assist in differentiation.
Differentiation from Glomerular or Microvascular Disease
Features of glomerular or microvascular disease include nephritic or nephrotic syndromes, with corresponding extrarenal manifestations (e.g., photosensitivity, hemoptysis, or abnormal immunological markers). Proteinuria is often significant, with striking hematuria and casts detected in urine. Renal dysfunction tends to develop over weeks and is rarely accompanied by complete anuria. Early renal biopsy can confirm the diagnosis.
Differentiation from Acute Interstitial Nephritis)
Typical features include a history of drug allergies or infections and symptoms such as significant flank pain. Drug-induced AIN may present with fever, rash, arthralgia, and eosinophilia. Renal biopsy aids in cases of diagnostic uncertainty.
Differentiation from Acute Renal Artery Occlusion or Renal Vein Thrombosis
Acute renal artery occlusion commonly occurs due to embolism, thrombosis, or aortic dissection, and less frequently from vasculitis or atherosclerosis. Embolism from a cardiac mural thrombus is a common cause. Acute renal vein thrombosis is rare and often associated with nephrotic syndrome, renal cell carcinoma, renal trauma, or severe dehydration in children with renal disease. Inferior vena cava thrombus formation may develop and present with inferior vena cava obstruction syndrome, severe lumbar pain, and hematuria. Renal vascular imaging can confirm the diagnosis.
Treatment
AKI is not a single disease, and its treatment depends on the underlying cause and type. General treatment principles include early identification and correction of reversible causes, maintaining fluid, electrolyte, and acid-base balance, promoting renal function recovery, providing appropriate nutritional support, preventing and managing complications, and initiating renal replacement therapy (RRT) when necessary.
Early Intervention for Underlying Causes
Early intervention during the initiation phase of AKI may minimize kidney damage and promote recovery of renal function. Efforts focus on discontinuing all nephrotoxic drugs, correcting reversible causes, and maintaining an appropriate volume status and perfusion pressure. This includes strategies such as volume expansion, stabilizing hemodynamics, addressing hypoproteinemia, reducing afterload to improve cardiac output, discontinuing medications that impair renal perfusion, and optimizing peripheral vascular resistance within the normal range.
AKI secondary to glomerulonephritis or small-vessel vasculitis often requires treatment with glucocorticoids and/or immunosuppressants. In cases with suspected acute interstitial nephritis (AIN), it is critical to identify and discontinue the offending drug promptly. When AIN is confirmed as drug-induced, early treatment with glucocorticoids is recommended.
For postrenal AKI, early relief of urinary tract obstruction is necessary. For example, prostatic hypertrophy can be managed with indwelling bladder catheterization, while tumors compressing the ureters may require ureteral stent placement or percutaneous nephrostomy.
Nutritional Support
Nutritional support is primarily delivered via the gastrointestinal tract (including enteral feeding) when feasible, with restrictions on water, sodium, and potassium intake as appropriate. For patients unable to take nutrients orally, parenteral nutrition is necessary. The total energy and nutrient composition should be adjusted based on clinical status. The total energy intake in all stages of AKI ranges from 20–30 kcal/(kg·d), consisting of carbohydrates at 3–5 g (up to a maximum of 7 g)/(kg·d), fats at 0.8–1.0 g/(kg·d), and proteins or amino acids at 0.8–1.0 g/(kg·d). For patients with high catabolic states or those undergoing RRT or continuous renal replacement therapy (CRRT), protein or amino acid intake should be adjusted accordingly. Intravenous lipid supplementation should include medium- and long-chain mixed emulsions, while amino acid supplementation should include both essential and non-essential amino acids. Blood glucose levels in critically ill patients should be maintained within a target range of 6.11–8.27 mmol/L (110–149 mg/dL).
Daily monitoring of fluid intake and output as well as weight changes is essential. The daily fluid replacement volume comprises visible fluid losses, insensible losses, minus endogenous water production. A rough estimation for fluid intake can be calculated as urine output from the previous day plus 500 ml. During RRT, fluid replacement requirements may be increased as needed.
Management of Complications
Close monitoring of Scr, blood urea nitrogen (BUN), and blood electrolyte levels is essential. Hyperkalemia is one of the leading causes of mortality in AKI, requiring urgent treatment when serum potassium exceeds 6 mmol/L, electrocardiographic changes of hyperkalemia are present, or symptoms affecting the nervous or muscular systems develop. Treatment strategies include:
- Discontinuing all potassium-containing drugs and/or foods.
- Counteracting the myocardial toxicity of potassium ions through intravenous administration of diluted 10% calcium gluconate.
- Facilitating the intracellular shift of potassium ions. This can be achieved by promoting glycogen synthesis via combined glucose and insulin administration [e.g., 50–100 ml of 50% glucose or 250–500 ml of 10% glucose with 6–12 units of regular insulin infused intravenously (glucose-to-insulin ratio of approximately 4:1)]. In cases of metabolic acidosis, bicarbonate administration can correct acidosis and concomitantly promote intracellular potassium shift (e.g., 250 ml of 5% NaHCO3 via intravenous infusion).
- Removing excess potassium using ion-exchange resins (oral agents act within 1–2 hours, while enemas act within 4–6 hours, with each 50 g dose reducing serum potassium by 0.5–1.0 mmol/L), selective potassium binders, loop diuretics (used to increase urine output and potassium excretion, though routine use of diuretics in AKI management is not recommended), or emergency dialysis (peritoneal dialysis exchanges approximately 5 mmol of potassium per liter per hour, while hemodialysis is the most effective method for rapidly reducing potassium levels). Repeated monitoring of serum potassium levels is necessary to adjust the treatment plan and prevent rebound hyperkalemia.
Metabolic acidosis is corrected as needed, with intravenous administration of 125–250 ml of 5% NaHCO3. In severe cases of acidosis, where venous bicarbonate levels are <12 mmol/L or arterial pH falls below 7.15–7.2, correction of acidosis should be coupled with emergency dialysis.
Heart failure in AKI patients often shows poor responsiveness to diuretics or digitalis preparations, and digitalis toxicity may occur readily. Vasodilators are commonly employed to reduce preload and alleviate symptoms. Dialysis with ultrafiltration to relieve fluid overload is the most effective approach to improving heart failure symptoms.
Infection is a frequent complication of AKI and a major cause of mortality. Early initiation of antibiotics is recommended, selecting agents with minimal renal toxicity based on bacterial cultures and sensitivity tests. Drug dosages should be adjusted according to creatinine clearance levels.
Renal Replacement Therapy (RRT)
RRT is an essential component of AKI treatment, encompassing modalities such as peritoneal dialysis, intermittent hemodialysis, and continuous renal replacement therapy (CRRT). The objectives of RRT in AKI include both "renal replacement" and "renal support."
The goal of "renal replacement" is to address life-threatening disturbances caused by significant kidney dysfunction. This primarily involves correcting severe fluid, electrolyte, acid-base imbalances, and azotemia. Indications for urgent dialysis include severe metabolic acidosis unresponsive to conservative medical treatment (arterial pH <7.2), hyperkalemia (potassium level >6.5 mmol/L or associated with serious arrhythmias), severe pulmonary edema unresponsive to diuretic therapy, and severe uremic symptoms such as encephalopathy, pericarditis, or seizures.
The goal of "renal support" is to stabilize the internal environment, remove inflammatory mediators, uremic toxins, and other pathogenic substances, prevent factors that could exacerbate renal damage, reduce renal workload, and promote recovery of renal function. This approach also supports the function of other organs and creates conditions for the treatment of primary disease and complications. For instance, RRT can help remove excess fluid in cases of congestive heart failure or eliminate large quantities of metabolic byproducts during tumor lysis syndrome induced by chemotherapy.
In cases of severe AKI, with life-threatening disturbances in fluid, electrolytes, or acid-base balance, early initiation of RRT is often preferred. The selection of an appropriate RRT modality is guided by the principles of safety, efficacy, simplicity, and cost-effectiveness. CRRT is particularly advantageous in patients with significant hemodynamic instability or acute brain injury. Targeted, goal-directed RRT is encouraged, which involves identifying the patient’s treatment needs, establishing specific objectives for RRT, and determining the timing, dosage, and modality of RRT based on these objectives. RRT parameters are dynamically adjusted during therapy based on therapeutic outcomes to achieve precise, goal-directed renal replacement therapy.
The therapeutic objectives of RRT in AKI include the following:
- Maintaining fluid, electrolyte, and acid-base balance.
- Preventing further renal damage.
- Promoting recovery of renal function.
- Enabling other treatments (e.g., antibiotics, nutritional support) without restrictions.
Recovery Phase Management
During the early recovery phase of AKI, life-threatening complications may persist. The focus of treatment remains on maintaining fluid, electrolyte, and acid-base balance, controlling azotemia, treating the primary disease, and preventing various complications. For certain patients with acute tubular necrosis (ATN) who experience prolonged polyuria, gradual reduction of fluid supplementation can help shorten the polyuric phase. Survivors of AKI require long-term follow-up and treatment based on CKD diagnostic and management guidelines.
Prognosis
The outcomes of AKI depend on the severity of the underlying disease and associated complications. Prerenal AKI often has an excellent prognosis, with kidney function frequently recovering to baseline levels if diagnosed and treated early, and the mortality rate is generally less than 10%. Postrenal AKI also tends to have a favorable prognosis when obstruction is relieved in a timely manner, particularly within two weeks, with most patients experiencing good recovery of renal function.
Conversely, the mortality rate in renal AKI ranges from 30% to 80%, depending on the severity of kidney injury. In some cases, renal function does not fully recover after AKI, especially in patients with pre-existing CKD, where the condition often fails to return to baseline levels and progresses more rapidly to end-stage renal disease (ESRD). For patients with underlying glomerulonephritis or vasculitis, the restoration of renal function is significantly influenced by the progression of the primary disease and may not always return to baseline levels.
Prevention
Given the persistently high incidence and mortality of AKI, prevention remains crucial. Key measures involve effective management of the primary disease, prompt elimination of AKI triggers, and correction of risk factors. The prevention and management of AKI should follow a stage-based approach. In high-risk patients who are exposed to or have already been affected by AKI triggers, targeted preventive measures may be necessary. These include timely correction of prerenal factors and stabilization of hemodynamics. For hemorrhagic shock, isotonic crystalloid solutions are preferred for fluid resuscitation, while vasopressors are used appropriately alongside volume expansion in cases of vasogenic shock. Abdominal compartment syndrome requires rapid alleviation of intra-abdominal hypertension.
It is vital to comprehensively evaluate the necessity of exposing high-risk patients to nephrotoxic drugs or procedures used for diagnostic or therapeutic purposes. Efforts should be made to minimize the use of nephrotoxic agents. When such drugs are unavoidable, adjustments to formulation, dosage, and administration should be made based on renal function to reduce nephrotoxicity, while renal function should be closely monitored.