bubble_chart Overview

Acute tubular necrosis (ATN) is the most common type of acute renal failure, accounting for approximately 75-80%. It is a clinical syndrome caused by various diseases leading to renal ischemia and/or nephrotoxic damage, resulting in rapid and progressive decline in renal function. The main manifestations include progressive azotemia due to a significant decrease in glomerular filtration rate, as well as water, electrolyte, and acid-base imbalances caused by impaired tubular reabsorption and excretion functions. Based on the presence or absence of reduced urine output, it can be classified into oliguric (anuric) and non-oliguric types. In treatment, early dialysis for severe cases can significantly reduce the incidence of infections, bleeding, and cardiovascular complications. The prognosis is related to factors such as the underlying disease, age, timing of diagnosis and treatment, and the presence of multiple organ failure. Some diseases causing acute tubular necrosis are preventable, and most cases are reversible. With timely treatment, renal function can fully recover within weeks or months.

bubble_chart Etiology

The main disease causes of acute tubular necrosis are traditionally divided into two major categories: acute renal ischemia and acute nephrotoxic injury. However, cases caused by intravascular hemolysis and certain infections are also not uncommon. Sometimes, renal ischemia and nephrotoxic factors can coexist.

(1) **Acute Renal Ischemia** Acute renal ischemia is the most common type of ATN, partly due to the persistent action and progression of the aforementioned prerenal factors, leading to prolonged renal ischemia and hypoxia, thereby causing ATN. Conditions such as massive bleeding or blood transfusion during or after major thoracic or abdominal surgeries, various causes of shock and post-shock recovery, cardiac resuscitation during extracorporeal circulation, restoration of renal blood circulation in kidney transplantation, and cardiac resuscitation all fall under renal ischemia-reperfusion conditions. Generally speaking, ischemic acute renal failure is more severe than other types of ATN, and the time required for renal function recovery is also longer.

(2) **Acute Nephrotoxic Injury** Nephrotoxic injury is mainly caused by exogenous nephrotoxins, such as drugs, heavy metals, chemical toxins, and biological toxins.

1. **Drug-Induced Nephrotoxic Injury** The incidence of this condition is currently on the rise, accounting for 11% of total acute renal failure cases and 17.1% of acute renal failure cases caused by internal medical conditions. Common drugs that cause ATN include aminoglycoside antibiotics (e.g., gentamicin, kanamycin, amikacin), polymyxin B, tobramycin, sulfonamides, amphotericin B, cyclosporine A, and cisplatin.

2. **Toxin-Induced Nephrotoxic Injury**

⑴ Heavy metal nephrotoxins: such as mercury, cadmium, arsenic, uranium, chromium, lithium, bismuth, lead, and platinum;

⑵ Industrial toxins: such as cyanide, carbon tetrachloride, methanol, toluene, ethylene glycol, and chloroform;

⑶ Disinfectants and antiseptics: such as cresol, resorcinol, and formaldehyde;

⑷ Pesticides and herbicides: such as organophosphates and paraquat. For these toxins, early measures to eliminate internal toxins should be taken.

3. **Biological Toxins** Examples include bile from black carp, snake bites, poisonous mushrooms, and bee venom. These toxins often lead to multiple organ failure, simultaneously damaging the lungs, kidneys, liver, and heart. During emergency treatment, maintaining the function of major organs is crucial.

4. **Contrast-Induced Renal Injury** Acute renal injury is more likely to occur in patients with pre-existing renal impairment, diabetes, elderly individuals, hypovolemia, hyperuricemia, and multiple myeloma.

(3) **Infectious Diseases** Diseases such as epidemic hemorrhagic fever and leptospirosis can cause ATN. Among these, hemorrhagic fever is the most common, accounting for 18.6% of total acute renal failure cases and 29% of internal medical causes. The pathological basis of hemorrhagic fever is systemic small vessel hemorrhagic damage, with a high mortality rate in severe cases. Early diagnosis and prompt dialysis treatment are emphasized.

(4) **Acute Hemolysis and Intravascular Hemolysis** Examples include incompatible blood transfusions, red blood cell destruction due to extracorporeal circulation, hemolytic anemia crises caused by immune diseases, hemoglobinuria from various causes, blackwater fever in malaria-endemic areas, severe malaria, and hemolysis induced by antimalarial drugs such as primaquine and quinine. Crush injuries, trauma, and non-traumatic rhabdomyolysis can lead to massive myoglobin deposition in renal tubules, causing kidney damage similar to that seen in hemolysis.

bubble_chart Pathogenesis

The pathogenesis of acute tubular necrosis (ATN) is multifaceted, with alterations in renal hemodynamics and acute tubular injury being the primary factors. The key points of various theories are outlined below:

(1) Alterations in Renal Hemodynamics Changes in renal hemodynamics play a dominant role in the early stages of ATN and are often the initiating factor. In hemorrhagic shock or severe hypovolemia, systemic blood redistribution occurs due to neural and humoral regulation, leading to renal vasoconstriction. This results in a significant reduction in renal blood flow, decreased renal perfusion pressure, and marked constriction of the afferent arterioles, causing renal cortical ischemia and the onset of ATN. In some cases, even after rapid blood volume restoration in the early stage of acute ischemic ATN due to massive hemorrhage, renal blood flow recovers, but the glomerular filtration rate (GFR) does not. This indicates that intrarenal hemodynamic changes and abnormal renal blood flow distribution are present early in ATN. The pathophysiological basis of these hemodynamic abnormalities is thought to be related to the following factors.

1. Role of Renal Nerves Renal sympathetic nerve fibers are widely distributed in renal blood vessels and the juxtaglomerular apparatus. Increased adrenergic activity induces renal vasoconstriction, leading to reduced renal blood flow and GFR. In ischemic ATN, renal vasoconstriction induced by renal nerve stimulation is far more pronounced than in normal animals, suggesting heightened vascular sensitivity to renal nerve stimulation in ATN. However, this enhanced response can be inhibited by calcium channel blockers, indicating that renal vasoconstriction due to nerve stimulation is related to changes in calcium activity in renal vascular smooth muscle. Clinically, however, the incidence of ischemic ATN in denervated kidneys, such as in allogeneic renal transplants after blood supply restoration, can be as high as 30%. This observation does not support a dominant role of renal nerves in the pathogenesis of ATN.

2. Role of Intrarenal Renin-Angiotensin System The kidney possesses a complete intrarenal renin-angiotensin system. In ischemic ATN, changes in renal blood circulation are largely attributed to the activation of this system, leading to intense constriction of the afferent arterioles. However, inhibiting renin activity or antagonizing angiotensin II does not prevent ATN, indicating that the renin-angiotensin system is not the decisive factor in ATN.

3. Role of Intrarenal Prostaglandins Intrarenal prostaglandins, particularly prostacyclin (PGI₂), are synthesized in the renal cortex and exhibit significant vasodilatory effects. They increase renal blood flow and GFR, promote natriuresis, and counteract the antidiuretic hormone's water reabsorption in the collecting ducts, thereby exerting a diuretic effect. It has been confirmed that PGI₂ levels in blood and renal tissues are markedly reduced in ATN. Studies have shown that intrarenal PGI₂ can prevent the onset of ischemic ATN, while the prostaglandin antagonist indomethacin exacerbates ischemic renal injury. Additionally, during renal ischemia, increased thromboxane synthesis in the renal cortex further promotes renal vasoconstriction. However, there is currently no evidence to suggest that prostaglandins play a dominant role in ATN.

4. The Role of Endothelial Cell-Derived Vasoconstrictive and Vasodilatory Factors in ATN For many years, numerous scholars have emphasized that the pathological increase in the secretion of endothelium-derived vasoconstrictive factors and the impaired release of endothelium-derived vasodilatory factors, such as nitric oxide (NO), play a significant role in the hemodynamic changes of ATN. They found that the reduction in renal blood flow during the early stages of ATN is not due to the action of renin-angiotensin but rather results from renal ischemia and hypoxia, which trigger the release of increased endothelin from vascular endothelial cells (experiments have shown that low concentrations of endothelin can cause intense and sustained vasoconstriction in renal vessels, increasing resistance in small renal vessels and leading to a decline or cessation of GFR. The glomerular capillaries, mesangial cells, and true small vessels exhibit a high density of endothelin receptors. Continuous experimental intrarenal infusion of endothelin also induces marked renal vasoconstriction). This leads to elevated resistance in both afferent and efferent arterioles, with the increase in afferent arteriolar resistance being more pronounced, resulting in a parallel decline in renal blood flow and GFR. However, in some cases, patients exhibit a tenfold increase in serum endothelin levels without developing clinical ATN. Normally, vascular endothelium can also release vasodilatory factors, which coordinately regulate blood flow to maintain circulation. In the kidneys, these factors increase blood flow and reduce resistance in both afferent and efferent arterioles. In the early stages of ATN, the release of endothelial vasodilatory factors is impaired, and the increased oxygen free radicals following ischemia-reperfusion further disrupt their release. Under these conditions, the hemodynamic changes in renal blood flow may become particularly prominent. Currently, it is believed that an imbalance in the regulation of endothelial-derived vasoconstrictive and vasodilatory factors may play a crucial role in the onset and progression of certain types of ATN.

5. Renal medulla static blood In the ischemic ATN model, it was also observed that the outer zone of the renal medulla and the inner zone of the cortex were the most severely damaged, and the degree of renal medulla static blood was significantly correlated with the severity of ATN damage. Medulla static blood hypoxia first affects the blood supply to the thick ascending limb tubular cells. Since the thick ascending limb is a high-energy-consuming area, it is exceptionally sensitive to hypoxia. Hypoxic tubular cells exhibit reduced ability to actively reabsorb sodium chloride. Injury to the thick ascending limb can lead to the easy deposition of T-H glycoprotein in the thick segment, causing distal tubular lumen obstruction and extravasation of luminal fluid. Therefore, it is believed that medulla static blood is also an important disease cause factor in ischemic ATN.

(2) Mechanism of renal ischemia-reperfusion cell injury After acute ischemia and hypoxia, when blood supply is restored to renal tissues—such as after shock correction, massive hemorrhage transfusion, extracorporeal circulation or cardiac resuscitation, or restoration of blood circulation in transplanted kidneys—a large number of oxygen free radicals are generated. During hypoxia, energy breakdown exceeds synthesis, leading to the accumulation of hypoxanthine, a breakdown product of adenosine triphosphate (ATP). Under the action of xanthine oxidase, this produces large amounts of xanthine, followed by increased generation of oxygen free radicals. Renal tissue cell membranes are rich in lipids, such as polyunsaturated fatty acids, which have a high affinity for free radicals, leading to the production of various lipid peroxides. These peroxides disrupt the balance between polyunsaturated fatty acids and proteins on the cell membrane, altering membrane fluidity and permeability. Consequently, cellular dysfunction occurs, enzyme activity decreases, capillary permeability significantly increases, and excessive exudation leads to cell and interstitial edema. Free radical-induced injury to the cell membrane also allows a large influx of extracellular calcium ions into the cell, increasing intracellular calcium levels and causing cell death. Additionally, during renal ischemia, cortical mitochondrial function is significantly impaired, further reducing ATP synthesis and diminishing ATP-dependent ion transport on the cell membrane. This leads to intracellular calcium accumulation, which in turn stimulates excessive calcium uptake by mitochondria. Excessive mitochondrial calcium content ultimately results in cell death. Calcium channel blockers can prevent the increase in intracellular calcium concentration, thereby preventing the occurrence of ATN.

(3) Acute tubular injury theory In severe crush injuries and acute toxic poisoning (e.g., caused by mercuric chloride or arsenic), the pathological changes in ATN primarily involve acute tubular cell sloughing, necrosis, and renal interstitial edema, while glomerular and vascular changes are relatively mild or absent. This suggests that the main mechanism of disease in ATN is due to primary tubular injury leading to a reduction or cessation of GFR. In 1975, Thurau et al. proposed that the decline in GFR during ATN is caused by the tubuloglomerular feedback mechanism triggered by acute tubular injury. In recent years, many scholars have further emphasized the critical role of tubular epithelial cell adhesion factors and polypeptide growth factors in the occurrence, progression, and tubular repair of ATN.

1. Theory of Renal Tubular Obstruction Toxins and other factors can directly damage renal tubular epithelial cells, with lesions uniformly distributed, primarily in the proximal tubules. Necrotic renal tubular epithelial cells, shed epithelial cells, microvilli debris, cellular casts, or hemoglobin and myoglobin can obstruct the renal tubules, leading to increased intraluminal pressure in the proximal tubules. This, in turn, elevates the pressure within the glomerular capsule. When the sum of this pressure and the colloid osmotic pressure approaches or equals the pressure in the glomerular capillaries, glomerular filtration ceases. Experimental evidence shows that sublethal renal tubular injury caused by renal ischemia or nephrotoxicity primarily manifests as shedding of the proximal tubule brush border, swelling of eyelid, and vacuolar degeneration. Renal tubular epithelial cells (TEC) detach from the basement membrane, creating defects or denuded areas on the tubular basement membrane. However, most of the shed TECs remain morphologically intact and viable. Similarly, in rabbit models of ischemic and toxic renal injury, the number of TECs in the urine significantly increases, indicating that TECs shed during ATN, with a considerable number remaining alive. Studies suggest that TEC detachment from the basement membrane results from altered cell adhesion. Among the family of renal tubular epithelial cell adhesion molecules, integrins have the most significant impact on ATN development. Integrins mediate cell-to-cell and cell-to-matrix adhesion, maintaining the structural integrity of renal tubules. Changes in cell adhesion during TEC injury include: ① Alterations in the cytoskeleton, particularly actin filaments, which play a crucial role in TEC adhesion to cells and the matrix. During renal tubular epithelial injury, cytoskeletal changes lead to TEC detachment from the basement membrane. ② Changes in integrins: Ischemia-reperfusion injury can cause significant abnormal redistribution of integrins, especially in uninjured tubular regions, where tubular epithelial cells lose their polarized integrin distribution. This suggests that reperfusion alters cell adhesion, and overexpression of integrins on injured cell surfaces may enhance cell-to-cell adhesion in the tubular lumen, promoting the formation of obstructive cellular aggregates. ③ Changes in matrix proteins: In 1991, Lin and Walker reported that 30–40 minutes after clamping the renal pedicle in experimental animals, semi-quantitative immunofluorescence analysis showed a grade I reduction in laminin. Three to four days after ischemic injury, laminin increased in the cortex and corticomedullary junction, while tenascin and fibronectin began to rise 1–2 days post-ischemia, peaking on day 5. Type IV collagen staining remained unchanged. These findings indicate significant early changes in matrix components during ischemic injury, which may affect TEC adhesion and relate to TEC shedding and post-injury repair. In summary, research on TEC adhesion mechanisms and their alterations in disease states is still in its early stages. Once these processes are elucidated, they will significantly impact the understanding of ATN pathogenesis. Understanding the mechanisms of epithelial cell shedding will help explore fundamental methods to prevent shedding, enhance repair, maintain the functional integrity of the epithelial system, and mitigate pathological injury.

2. Backflow theory This refers to the theory that after renal tubular epithelial injury leads to necrosis and shedding, defects and denuded areas appear on the tubular wall, allowing the tubular lumen to directly communicate with the renal interstitium. As a result, the primary urine in the tubular lumen backflows and diffuses into the renal interstitium, causing interstitial edema, compressing the nephron, exacerbating renal ischemia, and further reducing GFR. However, Donohoe et al. observed in experimental ATN that backflow of tubular fluid occurs only in cases of severe tubular necrosis. Other experiments have also demonstrated that the decline in renal blood flow and GFR can precede tubular fluid backflow, indicating that the latter is not the initiating factor in ATN. Nonetheless, the severity of renal interstitial edema during ATN is an important factor in disease progression.

3. Tubuloglomerular feedback mechanism Ischemia, nephrotoxicity, and other factors cause acute tubular injury, significantly reducing the reabsorption of sodium, chloride, and other solutes in the affected tubule segment. The increased concentration of sodium and chloride in the tubular lumen is sensed by the macula densa in the distal tubule, leading to increased renin secretion by the juxtaglomerular cells of the afferent arteriole. Subsequently, angiotensin I and II levels rise, causing constriction of the afferent arteriole and renal vasculature, increasing renal vascular resistance, and markedly reducing GFR. Additionally, the significant reduction in tubular blood supply decreases the release of renal prostaglandins into the cortex, further lowering renal blood flow and GFR.

4. Disseminated intravascular coagulation (DIC) ATN caused by sepsis, severe infections, epidemic hemorrhagic fever, shock, postpartum hemorrhage, pancreatitis, burns, and other conditions often involves diffuse microvascular damage. Platelets and fibrin deposit on the injured renal vascular endothelium, leading to vascular obstruction or impaired blood flow. Red blood cells passing through the damaged vessels are prone to deformation, fragmentation, and lysis, resulting in intravascular hemolysis. The increased platelet aggregation and vasospasm may also be related to reduced prostaglandin levels during renal ischemia. These disease causes often activate coagulation pathways and inhibit fibrinolysis, leading to microvascular thrombosis. DIC is generally considered a critical condition. It can serve as a cause of ATN but may also develop during the progression of ATN, potentially causing or exacerbating bilateral renal cortical necrosis. DIC is rare in uncomplicated ATN and thus cannot be regarded as a universal pathogenic mechanism of ATN.

Since the 1980s, significant progress has been made in understanding the pathogenesis of ATN. However, no single theory can yet explain all ATN phenomena. Different disease causes and types of tubular pathological damage may share common initiating mechanisms and perpetuating factors, and the various theories are interconnected and overlapping. Currently, a deeper understanding of the pathogenic mechanisms of ATN at each stage provides valuable guidance for early prevention and treatment.

bubble_chart Pathological Changes

The pathological histological damage site, nature, and extent of ATN vary depending on the disease cause and severity. The main pathological changes in the kidneys include enlargement, pallor, and increased weight; the cortical section appears pale, while the medulla is dark red. Light microscopy reveals degeneration, detachment, and necrosis of renal tubular epithelial cells. The lumens are filled with detached tubular epithelial cells, casts, and exudates. For cases caused by nephrotoxic substances, tubular lesions are mainly distributed in the proximal convoluted tubules. For example, mercury and gentamicin primarily affect the proximal end of the proximal convoluted tubule, while chlorate affects the middle and distal segments, and arsenicals may involve the entire proximal convoluted tubule. The degeneration and necrosis of epithelial cells mostly affect the cells themselves, with uniform distribution. The tubular basement membrane surface may be intact or defective, accompanied by interstitial edema, among other changes. Generally, around one week into the disease course, necrotic tubular epithelial cells begin to regenerate and quickly re-cover the basement membrane, gradually restoring the tubular morphology. In cases caused by renal ischemia, the terminal parts of the interlobular arteries are the earliest and most severely affected. Thus, tubular lesions in the cortical region, particularly in the ascending limb of the loop of Henle and the distal tubule, are most pronounced. Epithelial cells exhibit focal necrosis, and as ischemia worsens, the lesions spread to all segments of the tubule and the collecting ducts, resulting in highly uneven distribution. Lesions often appear segmental, scattered from the proximal convoluted tubule to the collecting ducts, with tubular epithelial cells showing necrosis, detachment, and fatty degeneration. In severely damaged areas, the tubular basement membrane may rupture or ulcerate, allowing luminal contents to enter the interstitium, causing interstitial edema, congestion, and inflammatory cell infiltration. Additionally, cortical vasoconstriction, medullary vascular dilation, and static blood are observed. If adjacent small veins are involved, thrombosis or interstitial hemorrhage may occur, leading to hematuria. In cases where the tubular epithelial basement membrane is severely damaged, cells often fail to regenerate, and the area is replaced by connective tissue hyperplasia, resulting in a prolonged recovery time for ischemic damage. Electron microscopy may reveal fragmentation and detachment of microvilli on the luminal surface of tubular epithelial cells, mitochondrial swelling, loss of cristae, and membrane rupture in tubular epithelial cells (TECs), as well as increased primary and secondary lysosomes and phagocytic vacuoles. In cases of severe TEC damage, disintegration and dissolution of organelles such as mitochondria and the Golgi apparatus may be observed, even leading to complete necrosis. In thrombotic microangiopathy-associated ATN, the renal microvasculature shows deposits of hyaline substances such as platelets and fibrin, obstructing the microvascular lumen. The damaged vessel walls often exhibit focal necrosis and inflammation. Glomeruli may show grade I mesangial cell proliferation and ischemic changes, even progressing to glomerulosclerosis. In rare cases, bilateral extensive necrosis of glomeruli and tubules in the renal cortex may occur.

bubble_chart Clinical Manifestations

The clinical manifestations of ATN include three aspects: the primary disease, metabolic disorders caused by acute renal failure, and complications.

The causes of ATN vary, and the initial manifestations also differ. Generally, the onset is abrupt, with obvious systemic symptoms. Based on the common patterns of clinical manifestations and disease progression, it is generally divided into three stages: the oliguric phase, the polyuric phase, and the convalescent stage.

(1) Oliguric or anuric phase

1. Decreased urine output: A sudden or gradual reduction in urine output, with daily urine volume persistently less than 400ml, is termed oliguria, while less than 50ml is termed anuria. Complete anuria is rare in ATN patients, and persistent anuria indicates a poorer prognosis, while also necessitating the exclusion of extrarenal obstruction and bilateral renal cortical necrosis. Due to varying causes and severity of the condition, the duration of oliguria differs. It generally lasts 1–3 weeks, but in some cases, oliguria may persist for over 3 months. It is generally believed that renal toxicity cases have a shorter duration, while ischemic cases last longer. If oliguria persists for more than 8–12 weeks, the diagnosis of ATN should be reconsidered, as renal cortical necrosis, pre-existing renal disease, or renal papillary necrosis may be present. For patients with prolonged oliguria, attention should be paid to fluid retention, congestive heart failure, hyperkalemia, hypertension, and the occurrence of various complications.

Non-oliguric ATN refers to cases where the patient maintains a daily urine output of more than 500ml, or even 1,000–2,000ml, during the progressive azotemia phase. The incidence of non-oliguric ATN has been increasing in recent years, reaching as high as 30–60%. This is attributed to increased recognition of this type, the widespread use of nephrotoxic antibiotics, and the early application of diuretics such as furosemide and mannitol. There are three explanations for the lack of reduced urine output: ① The degree of damage to nephrons varies, with some nephrons retaining renal blood flow and glomerular filtration function, while the corresponding tubular reabsorption function is significantly impaired; ② Although the degree of damage to all nephrons is similar, the impairment of tubular reabsorption is proportionally far greater than the reduction in glomerular filtration function; ③ The ability to form a hypertonic state in the deep renal medulla is reduced, leading to decreased water reabsorption from the filtrate in the loop of Henle. Common causes of non-oliguric ATN include long-term use of nephrotoxic drugs, major abdominal surgery, open-heart surgery, and hypoxic damage to transplanted kidneys. Generally, non-oliguric ATN is considered less severe than oliguric ATN, with shorter hospital stays, a lower percentage requiring dialysis, and fewer complications such as upper gastrointestinal bleeding. However, the incidence of hyperkalemia is similar to that in oliguric ATN, and the mortality rate of non-oliguric ATN can still be as high as 26%. Therefore, no aspect of treatment should be overlooked.

2. Progressive azotemia: Due to reduced glomerular filtration rate leading to oliguria or anuria, the excretion of nitrogenous and other metabolic waste products decreases, resulting in elevated plasma creatinine and blood urea nitrogen levels. The rate of increase is related to the state of protein catabolism in the body. In cases without complications and with proper treatment, the daily rise in blood urea nitrogen is relatively slow, approximately 3.6–7.1mmol/L (10–20mg/ml), while the plasma creatinine concentration rises by only 44.2–88.4µmol/L (0.5–1.0mg/ml). However, in hypercatabolic states, such as with extensive tissue trauma or sepsis, blood urea nitrogen may increase by 10.1mmol/L (30mg/ml) or more per day, and plasma creatinine may rise by 176.8µmol/L (2mg/ml) or more daily. Factors promoting excessive protein catabolism also include insufficient caloric intake, muscle necrosis, hematoma, gastrointestinal bleeding, fever due to infection, and the use of adrenal corticosteroids.

3. Water and electrolyte imbalances and acid-base disturbances

⑴Excessive water intake: Seen in cases where water control is not strict, intake or fluid replacement is excessive, and output such as vomiting, sweating, wound exudate is inaccurately estimated, or when endogenous water is overlooked during fluid replenishment calculations. As the oliguric phase prolongs, excessive water intake is more likely to occur, manifesting as dilutional hyponatremia, soft tissue edema, weight gain, hypertension, acute heart failure, and cerebral edema.

(2) Hyperkalemia: Normally, 90% of ingested potassium is excreted by the kidneys. During the oliguric phase of ATN, urinary potassium excretion decreases. If the body is in a hypercatabolic state—such as due to muscle necrosis from crush injuries, hematomas, infections, or insufficient caloric intake leading to protein breakdown and potassium release—or if acidosis causes intracellular potassium to shift extracellularly, severe hyperkalemia can develop within hours. If the patient is not promptly diagnosed and consumes potassium-rich foods or beverages, receives intravenous penicillin potassium salts (each 1 million units of penicillin potassium contains 1.6 mmol of potassium), or is transfused with large volumes of stored blood (blood stored for 10 days may contain up to 22 mmol of potassium per liter), hyperkalemia may be exacerbated or induced. In uncomplicated cases of ATN due to medical conditions, serum potassium typically rises by less than 0.5 mmol/L per day. Hyperkalemia can sometimes be insidious, with no specific clinical manifestations, or present with nausea, vomiting, paresthesia (such as limb numbness), bradycardia, and, in severe cases, neurological symptoms like fear, dysphoria, or apathy. In late stages, sinus or atrioventricular block, sinus arrest, intraventricular conduction block, or even ventricular fibrillation may occur. ECG changes often precede clinical symptoms of hyperkalemia, making ECG monitoring crucial for assessing its cardiac effects. Generally, when serum potassium reaches 6 mmol/L, the ECG shows tall, narrow-based T waves. As potassium levels rise further, P waves disappear, QRS complexes widen, the ST segment becomes indistinguishable, and eventually merges with the T wave, leading to severe arrhythmias and ventricular fibrillation. The cardiotoxic effects of hyperkalemia are also influenced by sodium, calcium levels, and acid-base balance. Concurrent hyponatremia, hypocalcemia, or acidosis can exacerbate clinical manifestations and increase the risk of arrhythmias. Notably, there may sometimes be discrepancies between serum potassium levels and ECG findings. Hyperkalemia is a common cause of death in oliguric patients, and early dialysis can prevent its occurrence. However, severe muscle necrosis may still lead to persistent hyperkalemia.

(3) Metabolic acidosis: Normally, the body produces 50–100 mmol of fixed acids daily, with 20% buffered by bicarbonate and 80% excreted by the kidneys. In acute renal failure, impaired excretion of acidic metabolites and reduced renal tubular acid secretion and bicarbonate reabsorption lead to varying degrees of plasma bicarbonate depletion, which worsens more rapidly in hypercatabolic states. Endogenous fixed acids primarily arise from protein breakdown, with smaller contributions from carbohydrate and fat metabolism. Phosphate and other organic anions accumulate in body fluids, increasing the anion gap. If metabolic acidosis persists uncorrected in prolonged oliguria, muscle catabolism accelerates. Additionally, acidosis lowers the ventricular fibrillation threshold, predisposing to ectopic rhythms. Hyperkalemia, severe acidosis, hypocalcemia, and hyponatremia are critical complications of acute renal failure. While these are less common in dialysis-treated cases, some patients still require pharmacological correction of metabolic acidosis between dialysis sessions.

(4) Hypocalcemia and hyperphosphatemia: In ATN, hypocalcemia and hyperphosphatemia are less pronounced than in chronic renal failure, though hypocalcemia has been reported as early as two days into oliguria. Concurrent acidosis often increases ionized calcium levels, masking typical hypocalcemic symptoms. Hypocalcemia is largely driven by hyperphosphatemia, as 60–80% of ingested phosphate is normally excreted in urine. During the oliguric phase of ATN, mild (grade I) hyperphosphatemia is common, but marked elevation is rare unless significant metabolic acidosis is present. Correcting acidosis may lower phosphate levels, necessitating vigilance for hypophosphatemia in patients receiving total parenteral nutrition.

⑸ Hyponatremia and hypochloremia: These two conditions often coexist. The causes of hyponatremia may include dilutional hyponatremia due to excessive water intake, loss through the skin or gastrointestinal tract (e.g., burns, vomiting, diarrhea), or sodium-depleted hyponatremia in non-oliguric patients who still respond to high-dose furosemide. Severe hyponatremia can lead to decreased blood osmotic pressure, causing water to infiltrate into cells, resulting in cellular edema. This manifests as acute cerebral edema symptoms, exacerbates acidosis, and clinically presents as fatigue, weakness, drowsiness or impaired consciousness, disorientation, or even hypotonic unconsciousness. Hypochloremia is commonly seen in cases of vomiting, diarrhea, or non-oliguric patients using large doses of loop diuretics, presenting with symptoms such as abdominal distension and fullness, shallow breathing, spasms, or other manifestations of metabolic alkalosis.

6. Hypermagnesemia: In healthy individuals, 60% of ingested magnesium is excreted through feces, and 40% is excreted in urine. Since both magnesium and potassium ions are major intracellular cations, serum potassium and magnesium levels often rise in parallel during ATN, with hypermagnesemia being more prominent in cases of muscle injury. Magnesium ions have a depressant effect on the central nervous system, and severe hypermagnesemia can lead to respiratory and myocardial depression, warranting vigilance. Electrocardiographic changes in hypermagnesemia may also manifest as prolonged P-R intervals and widened QRS complexes. When prolonged P-R intervals and/or widened QRS complexes persist after correcting hyperkalemia, hypermagnesemia should be suspected. Hyponatremia, hyperkalemia, and acidosis all exacerbate the myocardial toxicity of magnesium ions.

4. Cardiovascular Manifestations

(1) Hypertension: In addition to the neurohumoral factors during renal ischemia that promote the secretion of vasoconstrictive active substances, fluid overload due to excessive water intake can exacerbate hypertension. Hypertension is uncommon in the early stages of ATN, but if oliguria persists, approximately one-third of patients may develop mild to grade II hypertension, typically ranging from 18.62–23.94/11.97–14.63 kPa (140–180/90–110 mmHg), sometimes even higher. In severe cases, hypertensive encephalopathy may occur, particularly in pregnant patients, who require close monitoring.

(2) Acute pulmonary edema and heart failure: These are common causes of death during the oliguric phase, primarily due to fluid retention. However, factors such as hypertension, severe infections, arrhythmias, and acidosis also contribute. The incidence was higher in earlier years but has significantly decreased with measures like correcting hypoxia, controlling fluid intake, and early dialysis. Nevertheless, they remain common fatal complications in severe ATN. Close monitoring of pulmonary symptoms and signs is essential.

(3) Arrhythmias: In addition to hyperkalemia-induced sinus arrest, sinus standstill, sinoatrial block, varying degrees of atrioventricular block, bundle branch block, ventricular tachycardia, and ventricular fibrillation, arrhythmias such as premature ventricular contractions and paroxysmal atrial fibrillation may also occur due to viral infections or the use of digitalis.

(4) Pericarditis: The incidence was 18% in earlier years but has decreased to 1% with early dialysis. It typically presents as pericardial friction rub and chest pain, with large pericardial effusions being rare.

5. Gastrointestinal Manifestations: These are the earliest signs of ATN. Common symptoms include marked loss of appetite, nausea, vomiting, abdominal distension and fullness, hiccups, or diarrhea. The presence of gastrointestinal bleeding, jaundice, or other symptoms often indicates complications. In the early stages, when azotemia is not yet pronounced, gastrointestinal symptoms may also be related to the primary disease, electrolyte imbalances, or acidosis. Persistent, severe gastrointestinal symptoms often lead to significant metabolic disturbances, complicating treatment. Early-onset severe gastrointestinal symptoms suggest the need for prompt dialysis.

6. Neurological Manifestations: Mild cases may exhibit no neurological symptoms. Some patients may experience fatigue or mental sluggishness early on. If symptoms such as apathy, drowsiness, dysphoria, restlessness, or even unconsciousness appear early, this indicates severe disease, and dialysis should not be delayed. Neurological manifestations are associated with severe infections, epidemic hemorrhagic fever, certain heavy metal poisonings, severe trauma, or multi-organ failure.

7. Hematological Manifestations: Anemia is an early sign in some patients, with its severity closely related to the primary cause, disease duration, and the presence of bleeding complications. Severe trauma, significant blood loss after major surgery, hemolytic anemia, severe infections, and acute ATN often result in more severe anemia. If clinical signs of bleeding tendency, thrombocytopenia, consumptive coagulopathy, or fibrinolysis are present, this no longer represents early DIC.

(II) Polyuric Phase A daily urine output of 2.5L is termed polyuria. In the early diuretic phase of ATN, a gradual increase in urine output is commonly observed, and progressive polyuria is a sign of beginning renal function recovery. The daily urine output may double, reaching 1000ml by days 3–5 of the diuretic phase. However, renal function does not immediately recover upon entering the polyuric phase. Sometimes, despite a daily urine output exceeding 3L, the GFR remains at 10ml/min or below. In patients with hypercatabolism, plasma creatinine and blood urea nitrogen levels may continue to rise. Only when the GFR significantly increases does blood nitrogen gradually decline. Hyperkalemia may still occur in the early polyuric phase, and sometimes this phase can persist for 2–3 weeks or longer. Prolonged polyuria can lead to hypokalemia, dehydration, and hyponatremia. Additionally, during this phase, infections, cardiovascular complications, and upper gastrointestinal bleeding remain common risks. Close monitoring of water, electrolyte, and acid-base balance is essential during the polyuric phase.

(3) Stage of convalescence Depending on factors such as disease cause, severity of the condition, duration of the polyuric phase, complications, and age, ATN patients may exhibit significant variability in the early recovery stage. They may be asymptomatic, feel generally well, or experience constitutional weakness, lack of strength, and emaciation. When blood urea nitrogen and creatinine levels significantly decrease, urine output gradually returns to normal. Except for a few cases, glomerular filtration function mostly recovers to normal within 3 to 6 months. However, in some cases, tubular concentrating dysfunction may persist for over a year. If renal function does not recover persistently, it may indicate permanent damage to the kidneys.

bubble_chart Auxiliary Examination

(1) Blood Test: Understand the presence and degree of anemia to determine whether there is cavity bleeding or signs of hemolytic anemia. Observe red blood cell morphology for abnormalities such as deformed or fragmented red blood cells, nucleated red blood cells, increased reticulocytes, and/or hemoglobinemia—laboratory changes indicative of hemolytic anemia, which aid in diagnosing the disease cause.

(2) Urine Test: Urinalysis in ATN patients is crucial for diagnosis and differential diagnosis, but results must be interpreted in conjunction with clinical findings: ① Changes in urine volume: During the oliguric phase, daily urine output is below 400ml, while in non-oliguric cases, urine volume may be normal or increased. ② Routine urine test: The urine often appears turbid and dark in color, sometimes resembling soy sauce. Proteinuria is mostly (+) to (++), occasionally reaching (+++) to (++++), primarily consisting of small to medium-sized molecular proteins. The degree of proteinuria does not assist in diagnosing the disease cause. Urine sediment examination often reveals varying degrees of hematuria, with microscopic hematuria being more common. However, heavy metal poisoning may present with significant proteinuria and gross hematuria. Additionally, shed renal tubular epithelial cells, epithelial cell casts, granular casts, and varying levels of leukocytes may be observed, sometimes alongside pigment casts or leukocyte casts. ③ Reduced and fixed urine specific gravity, mostly below 1.015, due to impaired tubular reabsorption, preventing urine concentration. ④ Urine osmolarity below 350 mOsm/kg, with a urine-to-blood osmolarity ratio below 1.1. ⑤ Increased urinary sodium content, typically 40–60 mmol/L, due to reduced tubular sodium reabsorption. ⑥ Decreased urine urea-to-hematuria ratio, often below 10, as urinary urea excretion decreases while hematuria levels rise. ⑦ Decreased urine-to-serum creatinine ratio, often below 10. ⑧ Renal failure index is usually greater than 2, calculated as the ratio of urinary sodium concentration to the urine-to-serum creatinine ratio. The index rises due to increased sodium excretion, decreased creatinine excretion, and elevated serum creatinine. ⑨ Fractional excretion of sodium (FeNa), reflecting the kidney's sodium clearance capacity, expressed as a percentage of glomerular filtration rate: (Urine sodium/serum sodium ratio ÷ urine creatinine/serum creatinine ratio) × 100, i.e.:

U_Na is urine sodium, P_Na is serum sodium, V is urine volume, U_Cr is urine creatinine, P_Cr is serum creatinine, and GFR is glomerular filtration rate. ATN patients often have values >1, while those with prerenal oliguria typically have values <1.

The above urinary diagnostic indices (⑤ to ⑨) are commonly used to differentiate between prerenal oliguria and ATN. However, in clinical practice, these indices become unreliable and may show contradictory results in patients treated with diuretics or hypertonic medications, and thus should only serve as auxiliary diagnostic references.

(3) Glomerular filtration function tests: Serum creatinine (Scr) and blood urea nitrogen (BUN) concentrations, as well as their daily increase rates, are measured to assess the degree of functional impairment and the presence of hypercatabolism. In uncomplicated ATN caused by medical diseases, Scr typically rises by 40.2–88.4 µmol/L (0.5–1.0 mg/dL) daily, with most oliguric-phase values ranging between 353.6–884 µmol/L (4–10 mg/dL) or higher. BUN usually increases by about 3.6–10.7 mmol/L (10–30 mg/dL) daily, with most values between 21.4–35.7 mmol/L (60–100 mg/dL). In severe cases with prolonged oliguria and hypercatabolism, Scr may rise by >176.8 µmol/L (2 mg/dL) and BUN by >7 mmol/L daily. In crush injuries or muscle trauma, the rise in Scr may not parallel the rise in BUN.

(4) Blood gas analysis: This primarily assesses the presence, severity, and nature of acidosis, as well as hypoxemia. Blood pH, alkali reserve, and bicarbonate levels are often below normal, indicating metabolic acidosis. Arterial blood oxygen partial pressure is particularly critical; if it is below 8.0 kPa (60 mmHg) and cannot be corrected with oxygen therapy, pulmonary examination should be performed to rule out pneumonia or adult respiratory distress syndrome (ARDS). Dynamic blood gas analysis is essential for critically ill patients.

(5) Serum electrolyte tests: Serum electrolyte concentrations should be closely monitored during both the oliguric and polyuric phases, including potassium, sodium, calcium, magnesium, chloride, and phosphorus levels. During the oliguric phase, special attention should be paid to hyperkalemia, hypocalcemia, hyperphosphatemia, and hypermagnesemia. During the polyuric phase, monitor for hyperkalemia or hypokalemia, hyponatremia, hypochloremia, and hypokalemic hypochloremic alkalosis.

(6) Liver function tests: In addition to coagulation function, these tests evaluate hepatocyte necrosis and other dysfunctions, including transaminases, serum bilirubin, and serum albumin/globulin levels. Besides assessing the extent of liver damage, they also help determine whether acute renal failure is secondary to primary liver failure.

(7) Bleeding Tendency Examination ① Dynamic platelet count to assess whether there is a decrease and its extent. For patients with bleeding tendencies or critical conditions, relevant DIC laboratory tests should be conducted. Platelet function tests to determine whether platelet aggregation is increased or decreased; ② Prothrombin time, whether normal or prolonged; ③ Thromboplastin generation, whether normal or abnormal; ④ Fibrinogen levels, whether decreased or increased; ⑤ Presence or absence of increased fibrin degradation products (FDP). If bleeding tendencies occur during the oliguric phase of ATN, DIC should be suspected. In such cases, a decrease in platelet count, platelet dysfunction, and coagulation disorders may be observed, manifesting as consumptive hypocoagulability in the body. The latter is due to the consumption of large amounts of clotting factors by disseminated intravascular coagulation (DIC) and secondary fibrinolysis, presenting as hypofibrinogenemia and a significant increase in blood FDP concentration.

bubble_chart Diagnosis

(1) Blood test: Understand the presence and degree of anemia to determine whether there is cavity bleeding or hemolytic anemia. Observe changes in red blood cell morphology, such as deformed or fragmented red blood cells, nucleated red blood cells, increased reticulocytes, and/or hemoglobinemia, which are laboratory indicators of hemolytic anemia. This is helpful for diagnosing the

disease cause. (2) Urine test: Urinalysis in ATN patients is crucial for diagnosis and differential diagnosis, but the results must be interpreted in conjunction with clinical findings: ① Changes in urine volume: During the oliguric phase, daily urine output is below 400ml, while in non-oliguric cases, urine output may be normal or increased. ② Routine urine test: The appearance is often turbid with dark-colored urine, sometimes resembling soy sauce. Proteinuria is mostly (+) to (++), occasionally reaching (+++) to (++++), primarily consisting of small and medium-sized molecular proteins. The degree of proteinuria does not aid in diagnosing the {|disease cause|}. Urine sediment examination often reveals varying degrees of hematuria, with microscopic hematuria being more common. However, heavy metal poisoning may present with significant proteinuria and gross hematuria. Additionally, shed renal tubular epithelial cells, epithelial cell casts, granular casts, and varying levels of white blood cells may be observed, sometimes including pigment casts or white blood cell casts. ③ Reduced and fixed urine specific gravity, mostly below 1.015, due to impaired tubular reabsorption, preventing urine concentration. ④ Urine osmolality below 350mOsm/kg, with a urine-to-blood osmolality ratio below 1.1. ⑤ Increased urinary sodium content, typically 40–60mmol/L, due to reduced tubular sodium reabsorption. ⑥ Decreased ratio of urinary urea to hematuria, often below 10, as urinary urea excretion decreases while hematuria increases. ⑦ Decreased ratio of urinary creatinine to serum creatinine, usually below 10. ⑧ The renal failure index is often greater than 2, calculated as the ratio of urinary sodium concentration to the ratio of urinary creatinine to serum creatinine. This index rises due to increased sodium excretion, decreased urinary creatinine excretion, and elevated serum creatinine. ⑨ Fractional excretion of sodium (FeNa), reflecting the kidney's sodium clearance capacity, expressed as a percentage of glomerular filtration rate:

U_Na is urinary sodium, P_Na is serum sodium, V is urine volume, U_Cr is urinary creatinine, P_Cr is serum creatinine, and GFR is glomerular filtration rate. ATN patients often have values >1, while those with prerenal oliguria usually have values <1.

The above urine diagnostic indices (⑤ to ⑨) are commonly used to differentiate between prerenal oliguria and ATN. However, in clinical practice, these indices become unreliable and may show contradictory results in patients treated with diuretics or hypertonic medications, and thus should only serve as auxiliary diagnostic references.

(3) Glomerular filtration function tests: Serum creatinine (Scr) and blood urea nitrogen (BUN) concentrations, as well as their daily increase rates, are measured to assess the degree of functional impairment and the presence of hypercatabolism. In uncomplicated ATN caused by medical diseases, Scr typically rises by 40.2–88.4 µmol/L (0.5–1.0 mg/dL) daily, with most oliguric-phase values ranging between 353.6–884 µmol/L (4–10 mg/dL) or higher. BUN usually increases by about 3.6–10.7 mmol/L (10–30 mg/dL) daily, with most values between 21.4–35.7 mmol/L (60–100 mg/dL). In severe cases with prolonged oliguria and hypercatabolism, Scr may rise by >176.8 µmol/L (2 mg/dL) daily, and BUN by >7 mmol/L daily. In crush injuries or muscle trauma, the rise in Scr may not parallel the rise in BUN.

(4) Blood gas analysis: This primarily assesses the presence, severity, and nature of acidosis, as well as hypoxemia. Blood pH, alkali reserve, and bicarbonate levels are often below normal, indicating metabolic acidosis. Arterial blood oxygen partial pressure is particularly critical; if it is below 8.0 kPa (60 mmHg) and cannot be corrected with oxygen therapy, pulmonary evaluation is necessary to rule out pneumonia or adult respiratory distress syndrome (ARDS). Dynamic blood gas analysis is essential for critically ill patients.

(5) Blood electrolyte tests: Blood electrolyte concentrations should be closely monitored during both the oliguric and polyuric phases, including potassium, sodium, calcium, magnesium, chloride, and phosphorus levels. During the oliguric phase, special attention should be paid to hyperkalemia, hypocalcemia, hyperphosphatemia, and hypermagnesemia. During the polyuric phase, watch for hyperkalemia or hypokalemia, hyponatremia, hypochloremia, and hypokalemic hypochloremic alkalosis.

(6) Liver function tests: In addition to coagulation function, these tests evaluate the presence of hepatocyte necrosis and other dysfunctions, including transaminases, serum bilirubin, and serum albumin/globulin levels. Besides assessing the extent of liver damage, they also help determine whether acute renal failure is secondary to primary liver failure.

(7) Bleeding Tendency Examination ① Dynamic platelet count to assess whether there is a decrease and its extent. For patients with bleeding tendencies or critical conditions, relevant DIC laboratory tests should be conducted. Platelet function tests to determine whether platelet aggregation is increased or decreased; ② Prothrombin time normal or prolonged; ③ Thromboplastin generation normal or abnormal; ④ Fibrinogen levels decreased or increased; ⑤ Presence or absence of increased fibrin degradation products (FDP). If bleeding tendencies occur during the oliguric phase of ATN, DIC should be suspected. In such cases, a decrease in platelet count, platelet dysfunction, and coagulation disorders may be observed, manifesting as consumptive hypocoagulability in the body. The latter is due to the consumption of large amounts of clotting factors by disseminated intravascular coagulation and secondary fibrinolysis, presenting as hypofibrinogenemia and a significant increase in blood FDP concentration.

bubble_chart Treatment Measures

(I) Treatment of the oliguric phase The oliguric phase is often complicated by acute pulmonary edema, hyperkalemia, upper gastrointestinal bleeding, and concurrent infections, which can lead to death. Therefore, the focus of treatment is to regulate water, electrolyte, and acid-base balance, control nitrogen retention, provide appropriate nutrition, prevent complications, and treat the underlying disease.

1. Bed rest All ATN patients should remain on bed rest.

2. Diet For patients who can eat, gastrointestinal nutrition should be prioritized, with a focus on light liquid or semi-liquid foods. Water, sodium, and potassium intake should be restricted as appropriate. Protein intake should be limited in the early stages (high biological value protein at 0.5g/kg). Severe ATN patients often exhibit significant gastrointestinal symptoms, so gastrointestinal nutrition should not be rushed. The first step is to allow the patient's gastrointestinal tract to adapt, aiming to restore gastrointestinal function while avoiding abdominal distension and fullness or diarrhea. Gradually, partial caloric intake can be supplemented at a rate of 2.2–4.4 kJ/d (500–1000 kcal). Excessive or rapid food supplementation often leads to poor absorption and diarrhea. Based on the allowable fluid intake, amino acid and glucose solutions can be supplemented to provide 6.6–8.7 kJ/d (1500–2000 kcal) to reduce protein catabolism. If the patient requires more than 6.6 kJ/d (1500 kcal), continuous blood filtration should be considered to ensure the necessary daily fluid intake.

3. Maintaining fluid balance Patients in the oliguric phase should strictly monitor 24-hour fluid intake and output. The 24-hour fluid replacement volume is the sum of measurable and insensible fluid losses minus endogenous water production. Measurable fluid loss refers to the total volume of urine, feces, vomiting, sweating, drainage, and wound exudate in the previous 24 hours. Insensible fluid loss refers to water lost through respiration (approximately 400–500 ml) and skin evaporation (approximately 300–400 ml). However, estimating insensible fluid loss is often difficult, so it can also be calculated as 12 ml/kg, taking into account body temperature, ambient temperature, and humidity. Generally, for every 1°C increase in body temperature, the hourly water loss is 0.1 ml/kg. If the room temperature exceeds 30°C, for every 1°C increase, insensible fluid loss increases by 13%. Difficulty breathing or tracheostomy increases respiratory water loss. Endogenous water refers to the total water produced by tissue metabolism, food oxidation, and glucose oxidation in fluids over 24 hours. The water produced by food oxidation is calculated as 0.43 ml per gram of protein, 1.07 ml per gram of fat, and 0.55 ml per gram of glucose. Since endogenous water production is often overlooked and insensible fluid loss is estimated, the accuracy of fluid replacement in the oliguric phase is affected. Therefore, the principle of "replace output with input, preferably less than more" has been adopted to prevent fluid overload. However, it is essential to consider whether hypovolemia is present to avoid excessive fluid restriction, which may worsen ischemic kidney damage and prolong the oliguric phase. The following indicators can be used to assess appropriate fluid replacement: ① No subcutaneous dehydration or edema; ② No daily weight gain—if weight increases by 0.5 kg or more, it suggests fluid overload; ③ Normal serum sodium concentration—if low without salt loss, it indicates fluid retention; ④ Central venous pressure between 0.59–0.98 kPa (6–10 cmH₂O)—if above 1.17 kPa (12 cmH₂O), it suggests fluid overload; ⑤ Normal vascular shadow on chest X-ray—if pulmonary congestion is present, it indicates fluid retention; ⑥ Rapid heart rate, elevated blood pressure, and increased respiratory rate without signs of infection may suggest fluid overload.

4. Management of Hyperkalemia The most effective methods are hemodialysis or peritoneal dialysis. In cases of severe hyperkalemia or hypercatabolic states, hemodialysis is preferable. Hyperkalemia is a clinical emergency, and emergency treatment should be administered while preparing for dialysis: ① Intravenous injection of 80–320 ml of 11.2% sodium lactate; for patients with metabolic acidosis, 250 ml of 5% sodium bicarbonate can be administered intravenously; ② Intravenous injection of 10 ml of 10% calcium gluconate to counteract the toxic effects of potassium ions on the myocardium; ③ Intravenous infusion of 200 ml of 25% glucose solution with 16–20 U of insulin to promote the transfer of glucose and potassium ions into cells for glycogen synthesis. However, this method is often limited in ATN patients due to oliguria restricting fluid intake; ④ Oral administration of 15–20 g of sodium-type ion-exchange resin mixed with 100 ml of 25% sorbitol solution, 3–4 times daily. Since ion-exchange resins act slowly, they are not suitable for emergency potassium reduction but are effective for preventing and treating non-hypercatabolic hyperkalemia. One gram of resin can adsorb 1 mmol of potassium ions. Additionally, restricting high-potassium foods, correcting acidosis, avoiding transfusions of stored blood, and removing necrotic tissue are all important measures for managing hyperkalemia. For crush injury patients with uncontrollable hyperkalemia, careful and thorough debridement of deep necrotic muscle is essential—only by removing necrotic tissue can hyperkalemia be controlled.

5. Metabolic Acidosis In the oliguric phase of non-high catabolic metabolism, providing sufficient calories and reducing tissue breakdown generally result in mild metabolic acidosis. However, high catabolic metabolic acidosis occurs early, is severe, and can sometimes be difficult to correct. Severe acidosis can exacerbate hyperkalemia and should be treated promptly. When the actual plasma bicarbonate level falls below 15 mmol/L, 100–250 ml of 5% sodium bicarbonate should be administered intravenously, with the infusion rate adjusted based on cardiac function, and dynamic follow-up monitoring of blood gas analysis. Sometimes, up to 500 ml (containing 60 mmol/L of sodium salts) may need to be supplemented daily. Therefore, severe metabolic acidosis should be addressed with hemodialysis as early as possible, as it is a safer method for correcting acidosis.

6. Use of Furosemide and Mannitol For ATN oliguric cases, after ruling out hypovolemia, furosemide can be tried. Furosemide dilates blood vessels, reduces renal vascular resistance, increases renal blood flow and glomerular filtration rate, and regulates intrarenal blood distribution, alleviating tubular and interstitial edema. Early use may prevent acute renal failure and reduce the likelihood of acute tubular necrosis. For oliguric acute renal failure, furosemide can also help differentiate between functional and organic causes. Intravenous injection of 4 mg/kg furosemide, with a significant increase in urine output within one hour, suggests a functional etiology. However, there is no consensus on the standard dose, and whether high-dose efficacy still indicates a functional cause remains debated. The author recommends an intravenous infusion of 200–400 mg, discontinuing further administration if ineffective after one attempt. Some reports suggest doses exceeding 1 g or even 4 g daily can induce diuresis, but such high doses may damage renal parenchyma and prolong recovery time. With the widespread availability of blood purification techniques, early dialysis is indicated for diuretic-resistant cases. Overreliance on furosemide to increase urine output also raises the risk of ototoxicity.

Mannitol, as an osmotic diuretic, can be used to prevent ATN from various causes, such as forced diuresis in cases of crush injury with resolved shock but persistent anuria, or to differentiate prerenal factors from acute renal failure-induced oliguria. The recommended method is intravenous infusion of 100–200 ml of 20% mannitol. If no increase in urine output occurs within one hour or if ATN-related oliguria (anuria) is confirmed, mannitol should be discontinued to avoid hypervolemia, which may precipitate heart failure or pulmonary edema.

7. Infection Since the introduction of early preventive dialysis, deaths from acute pulmonary edema and hyperkalemia during the oliguric phase have significantly decreased, with infection now being the leading cause of mortality. Common sites include the bloodstream, lungs, urinary tract, and biliary system. Antibiotic selection should be based on bacterial culture and sensitivity tests, prioritizing agents with minimal nephrotoxicity. Dosage adjustments for antimicrobial drugs in acute renal failure must also be carefully considered.

8. Nutritional Support Patients with acute renal failure, especially those with sepsis, severe trauma, or multiple organ failure accompanied by a hypercatabolic state, often experience daily breakdown of over 200g of endogenous proteins. Therefore, if the oliguric phase is prolonged and daily caloric intake is insufficient, it will inevitably lead to rapid progression of azotemia and hyperkalemia. Nutritional support can provide adequate calories, reduce endogenous protein breakdown, thereby slowing the rise in blood nitrogen levels, enhancing the body's resistance, lowering mortality during the oliguric phase, and potentially reducing the frequency of dialysis. Nutritional supplementation should, as much as possible, utilize the gastrointestinal tract to gradually increase caloric intake. However, critically ill patients often experience gastrointestinal symptoms or require partial or total parenteral caloric supplementation due to post-surgical conditions. Approximately two-thirds of the calories should be provided by hypertonic glucose, with the remaining one-third supplied by lipids. However, further research is needed to determine whether acute renal failure patients can tolerate emulsified fats and their maximum dosage. Nitrogen sources should be supplemented primarily with essential amino acids. Each unit of intravenous nutritional solution is 750ml, containing 250ml of amino acids (including eight essential amino acids, with a total nitrogen content of 1.46g), 500ml of 25–50% glucose, various vitamins, and an appropriate amount of insulin. Blood glucose levels should be monitored. For patients who can tolerate fluid supplementation, 500ml of 10% emulsified fat (Intralipid) may also be administered, providing 500 kcal. Each intravenous infusion should last at least 4 hours, as too rapid administration may cause gastrointestinal symptoms or other potential adverse effects. Blood electrolytes should be monitored during use. In patients without a hypercatabolic state, hypokalemia and hypophosphatemia often occur after several days of treatment, so appropriate supplementation should be given to avoid symptomatic hypokalemia and hypophosphatemia. Cases not undergoing dialysis often struggle to achieve adequate intravenous nutritional support, and special attention must be paid to volume-overload heart failure. For patients urgently requiring total parenteral nutritional support, continuous arteriovenous hemofiltration must be performed to ensure a daily fluid intake of over 5L.

9. Hemodialysis or peritoneal dialysis　Early preventive hemodialysis or peritoneal dialysis can reduce life-threatening complications such as infection, bleeding, or unconsciousness in acute renal failure. Preventive dialysis refers to performing dialysis before complications arise, which rapidly clears excessive metabolic products from the body, maintains water, electrolyte, and acid-base balance, thereby helping to preserve cellular physiological functions and the stability of the internal environment, as well as treating and preventing various complications of the primary disease.

Indications for emergency dialysis: ① Acute pulmonary edema or congestive heart failure; ② Severe hyperkalemia, with serum potassium above 6.5 mmol/L, or electrocardiogram showing significant ectopic rhythms accompanied by QRS wave widening.

General indications for dialysis: ① Oliguria or anuria lasting more than 2 days; ② Presence of uremic symptoms such as vomiting, mental apathy, dysphoria, or drowsiness; ③ Hypercatabolic state; ④ Signs of fluid retention; ⑤ Blood pH below 7.25, serum bicarbonate below 15 mmol/L, or CO₂ combining power below 13 mmol/L; ⑥ Blood urea nitrogen above 17.8 mmol/L (50 mg/dl), excluding purely extrarenal causes, or serum creatinine above 442 µmol/L (5 mg/dl); ⑦ For non-oliguric patients, dialysis should also be performed if any of the following occur: excessive fluid retention, conjunctival edema, gallop rhythm, central venous pressure higher than normal, serum potassium above 5.5 mmol/L, or electrocardiographic suspicion of hyperkalemia.

The choice between hemodialysis and peritoneal dialysis primarily depends on the clinical experience of the medical institution. However, hemodialysis is preferred in the following situations: patients with a hypercatabolic state, recent abdominal surgery (especially with drainage), or respiratory distress. Peritoneal dialysis is suitable for cases involving active bleeding or trauma, difficulty in establishing vascular access, elderly patients, unstable cardiovascular function, or pediatric cases.

Application of peritoneal dialysis in acute renal failure with heart failure: For patients with heart failure and fluid retention, a 2.5%–4.25% glucose dialysis solution may be selected based on the severity of heart failure and the required ultrafiltration rate, with 3% being the general standard. Each instillation of 2 L is retained for 30 minutes. Using a 4% glucose dialysis solution can remove 300–500 mL of fluid per session, and performing 10 sessions within 10 hours can achieve an ultrafiltration of 3 L. However, this may lead to hyperglycemia or even hyperosmolar unconsciousness, so it is only suitable for emergency treatment of acute pulmonary edema. A 2.5% glucose dialysis solution can achieve an ultrafiltration rate of 100–300 mL per hour, with 5 sessions removing approximately 1 L, making it suitable for mild or grade II heart failure. If the condition is severe and fluid removal is inadequate, switch to isolated ultrafiltration or CAVH immediately. When using a hypertonic 4.25% glucose dialysis solution, blood glucose levels must be closely monitored, especially in diabetic, prediabetic, or elderly patients. If blood glucose exceeds 300 mg/dl, switch to a 2% glucose dialysis solution and administer intraperitoneal insulin. For diabetic patients, intraperitoneal insulin injections should also be added. The recommended insulin doses are 4–5 U/L for 1.5%, 5–7 U/L for 2.5%, and 7–10 U/L for 4.25%, adjusted based on blood glucose levels. Insulin should not be added in the final dialysis session. During treatment, patients without a hypercatabolic state should also be monitored for hypokalemia. Even with 4 mmol/L of potassium chloride added to the dialysate, potassium deficiency may still occur, especially after correcting metabolic acidosis. Therefore, close follow-up of electrocardiograms and serum potassium levels is essential to prevent severe potassium deficiency-related arrhythmias and cardiac arrest.

10. Continuous Arteriovenous Hemofiltration (CAVH) is characterized by its simple operation and continuous low-flow replacement of glomerular