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Acute uric acid nephropathy
Acute uric acid nephropathy
Acute uric acid nephropathy
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Acute uric acid nephropathy
SpecialtyNephrology

Acute uric acid nephropathy (AUAN, also acute urate nephropathy) is a rapidly worsening (decreasing) kidney function (acute kidney injury) that is caused by high levels of uric acid in the urine (hyperuricosuria).

Causes

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Acute uric acid nephropathy is usually seen as part of the acute tumour lysis syndrome in patients undergoing chemotherapy or radiation therapy for the treatment of malignancies with rapid cell turnover, such as leukemia and lymphoma. It may also occur in these patients before treatment is begun, due to spontaneous tumor cell lysis (high incidence in Burkitt's lymphoma).

Acute uric acid nephropathy can also be caused by an acute attack of gout.

Pathophysiology

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Acute uric acid nephropathy is caused by deposition of uric acid crystals within the kidney interstitium and tubules, leading to partial or complete obstruction of collecting ducts, renal pelvis, or ureter. This obstruction is usually bilateral, and patients follow the clinical course of acute kidney failure.

Diagnosis

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The picture of acute kidney failure is observed: decreased urine production and rapidly rising serum creatinine levels. Acute uric acid nephropathy is differentiated from other forms of acute kidney failure by the finding of a urine uric acid/creatinine ratio > 1 in a random urine sample.

Prevention

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Patients at risk for acute uric acid nephropathy can be given allopurinol or rasburicase (a recombinant urate oxidase) prior to treatment with cytotoxic drugs.

Treatment

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Treatment is focused on preventing deposition of uric acid within the urinary system by increasing urine volume with potent diuretics such as furosemide. Raising the urinary pH to a level higher than 7 (alkalinization) is often difficult to attain, although sodium bicarbonate and/or acetazolamide are sometimes used in an attempt to increase uric acid solubility.

Dialysis (preferably hemodialysis) is started if the above measures fail.

References

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Revisions and contributorsEdit on WikipediaRead on Wikipedia

Acute uric acid nephropathy

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from Grokipedia
Acute uric acid nephropathy is a form of characterized by the rapid precipitation of uric acid crystals within the renal tubules and collecting ducts, resulting in oliguric or anuric renal failure. This condition most commonly arises in the context of following or for hematologic malignancies such as or , where massive cell destruction leads to acute . The pathophysiology involves overproduction and overexcretion of from the of nucleic acids released by lysed tumor cells, leading to in the distal , particularly when is acidic (below 5.5). Crystal deposition causes mechanical obstruction of the tubules, increased intratubular pressure, reduced , and secondary inflammation via activation of the and release of cytokines. Less common causes include severe tissue from other conditions, such as , epileptic seizures, or genetic disorders like Lesch-Nyhan syndrome, though these are rare without underlying . Clinically, patients present with sudden-onset , often within days of initiating cytotoxic therapy, accompanied by elevated serum levels (typically >15 mg/dL), , , and as part of . Diagnosis is supported by clinical history, high serum , and a urine -to-creatinine ratio greater than 1.0 in a spot urine sample, which helps differentiate it from other causes of acute renal failure; , if performed, shows intratubular crystals as needle-shaped structures with negative under polarized light. The incidence is up to 10% in high-risk patients without prophylaxis, but it has decreased significantly with preventive measures. Management focuses on prevention in at-risk patients through aggressive hydration (3-5 L/m²/day of intravenous fluids) and pharmacologic intervention with inhibitors like (300-600 mg/day) or recombinant urate oxidase (, 0.2 mg/kg IV daily) started 24-72 hours before therapy. For established cases, supportive care includes to promote , and if severe or derangements persist, with excellent and reversibility when treated promptly.

Background

Definition

Acute uric acid nephropathy is defined as a form of characterized by the precipitation of crystals within the renal tubules, resulting in tubular obstruction and subsequent oliguric or anuric renal failure. This condition arises from acute , where levels exceed the threshold in the renal tubules, leading to crystal formation and blockade of urine flow. Unlike chronic urate nephropathy, which involves the gradual interstitial deposition of monosodium urate over years without causing acute renal , acute uric acid nephropathy presents as a rapid-onset obstructive process distinct from isolated , which alone does not precipitate or renal impairment. Chronic urate nephropathy is associated with long-term leading to progressive kidney damage, whereas the acute form is triggered by sudden surges in . The condition is primarily associated with but can also occur in other states of rapid cellular turnover that accelerate catabolism. In humans, serves as the end product of due to the evolutionary loss of functional uricase enzyme, which in other mammals further degrades to for excretion. This absence results in higher baseline concentrations, predisposing humans to crystal precipitation under conditions of acute overload.

Epidemiology

Acute uric acid nephropathy, a renal complication of (TLS), primarily occurs in patients undergoing for hematologic malignancies, with clinical TLS incidence ranging from 3% to 20% in acute leukemias and lymphomas without prophylactic measures. In specific subtypes, such as , clinical TLS rates reach approximately 5%, while higher incidences of up to 15% are observed in bulky or high-burden diseases like or . The condition is rare in solid tumors, where TLS and associated nephropathy are mostly limited to case reports involving aggressive or metastatic cases. Globally, acute uric acid nephropathy is more prevalent in developed countries owing to the widespread use of intensive cancer therapies. Demographically, it disproportionately affects males, who exhibit higher baseline serum uric acid levels predisposing them to crystal precipitation in renal tubules. The typical age of onset aligns with peak hematologic diagnoses, predominantly between 50 and 70 years, though pediatric cases occur in aggressive leukemias. However, this is offset by a rising occurrence linked to targeted therapies, including in and , where TLS reports have increased, with accounting for over 10% of pharmacotherapy-associated cases.

Etiology and Pathogenesis

Causes

Acute uric acid nephropathy primarily arises from conditions that cause massive release of purine metabolites, leading to acute and subsequent renal tubular precipitation of crystals. The most common trigger is (TLS), which occurs due to rapid destruction of tumor cells, often induced by , , or spontaneous cell breakdown in high-burden malignancies. Specific examples include aggressive hematologic cancers such as and , where TLS incidence can exceed 5-17% depending on tumor burden and white blood cell count. In these cases, the breakdown of nucleic acids from lysed cells results in elevated serum levels, typically exceeding 15 mg/dL, predisposing to nephropathy. Other causes include massive , where muscle cell necrosis releases purines, contributing to alongside myoglobin-induced tubular damage, particularly in settings like crush injuries or severe seizures. Severe acute flares can also precipitate episodes through sudden surges in production and crystallization in renal tubules, often in patients with longstanding . Excessive alcohol intake represents another precipitant, as it induces , which competitively inhibits renal secretion and exacerbates . Non-oncologic causes are rare but encompass hemolytic anemias, where intravascular leads to purine overload from erythrocyte breakdown, mimicking TLS; genetic disorders such as Lesch-Nyhan , which result in excessive production; and high-dose ingestion, such as from excessive consumption of purine-rich foods or supplements, though this is uncommon without underlying predisposition. Several risk modifiers amplify the likelihood of developing acute uric acid nephropathy in the presence of . reduces volume, concentrating and promoting crystal formation in the tubules. Acidic pH below 5.5 further decreases solubility, facilitating precipitation, while pre-existing impairment limits excretion and heightens vulnerability to acute insults.

Pathophysiology

Acute uric acid nephropathy arises from the of in the renal tubular fluid, which promotes the precipitation of crystals primarily within the distal tubules and collecting ducts. This process is triggered by a rapid surge in serum levels, often exceeding 15 mg/dL, leading to elevated urinary concentrations that surpass the threshold. The undissociated form of , predominant in acidic environments, facilitates this , as is far less soluble than its ionized urate counterpart. These crystals aggregate to form casts that obstruct the intratubular lumen, causing mechanical blockage and subsequent backpressure within the . The obstruction elevates intratubular and intrarenal pressures, which in turn increases renal and diminishes renal blood flow. This hemodynamic alteration culminates in a marked reduction in the (GFR), precipitating . In addition to mechanical effects, the deposited crystals elicit an inflammatory cascade by activating the inflammasome in renal tubular cells and resident macrophages. This activation leads to the assembly of the inflammasome complex, resulting in caspase-1-mediated cleavage and release of pro-inflammatory such as interleukin-1β (IL-1β) and IL-18. The ensuing inflammation amplifies tubular injury through recruitment of immune cells and further cytokine production, exacerbating the renal damage beyond mere obstruction. Urine pH plays a critical role in modulating uric acid solubility, with low pH (typically <5.5) favoring the precipitation of undissociated uric acid due to its pKa of approximately 5.75. Solubility increases markedly with rising pH; for instance, at pH >6.5, uric acid solubility can rise more than 10-fold compared to acidic conditions, shifting the equilibrium toward the more soluble urate form. Acute uric acid nephropathy represents a kidney-specific manifestation of severe systemic hyperuricemia, commonly associated with , where these mechanisms converge to cause renal failure.

Clinical Presentation

Signs and Symptoms

Acute uric acid nephropathy primarily manifests as with or , characterized by urine output less than 400 mL per day due to intratubular obstruction by crystals. , resulting from distension of the renal tubules and collecting ducts, is a frequent complaint in affected patients. Systemic symptoms arise from the underlying and include fatigue, nausea, vomiting, lethargy, and secondary to fluid retention and . When occurs in the setting of —a common precipitant following —associated disturbances such as may induce cardiac arrhythmias, while can lead to neuromuscular and ; however, the renal-specific hallmark remains with elevated serum . Symptoms typically emerge 12 to 72 hours after the triggering event, such as initiation in patients with hematologic malignancies. Physical examination often reveals upon percussion, reflecting renal capsular irritation, and may develop due to from impaired renal excretion.

Complications

Acute uric acid nephropathy can lead to immediate complications such as resulting from prolonged intratubular obstruction by crystals, which impairs renal function and may cause irreversible damage if not promptly resolved. This obstruction often stems from the precipitation of in the distal tubules and collecting ducts, exacerbating in the context of (TLS). Systemic effects include significant imbalances, such as commonly associated with TLS, which can precipitate deposition and further renal damage. Severe cases may also involve seizures due to from accumulated toxins or secondary to , alongside the risk of multi-organ failure driven by widespread metabolic derangements and hypoperfusion. Renal-specific sequelae encompass progression to (CKD) in instances of recurrent or unresolved episodes, where sustained tubular injury leads to long-term (GFR) decline. Additionally, rare formation of uric acid stones can occur due to persistent , potentially causing further obstructive nephropathy. Mortality risk remains elevated in severe TLS-associated cases without timely intervention, reaching up to 21% primarily from cardiac arrhythmias due to or secondary infections like . Recent insights highlight increased recognition of hyperuricemia's role in , which may contribute to cardiovascular complications such as atherosclerosis acceleration and heightened risk of acute events in patients with .

Diagnosis

Diagnostic Criteria

Diagnosis of acute uric acid nephropathy (AUAN) relies on a combination of clinical context, laboratory findings indicative of and (AKI), and supportive imaging, with serving as the definitive but infrequently performed confirmatory test. AUAN is suspected in patients with marked , often in the setting of (TLS) or other massive release, presenting with oliguric AKI due to intratubular crystal precipitation. Laboratory criteria are central to establishing the . Serum uric acid levels exceeding 15 mg/dL (890 μmol/L), and sometimes reaching 50 mg/dL, reflect severe driving crystal formation. A urine uric acid-to-creatinine ratio greater than 1.0 distinguishes AUAN from other causes of AKI, as it indicates high overwhelming tubular solubility. The fractional of (FEUA) typically surpasses 10%, signifying intrinsic renal involvement rather than prerenal , where FEUA is usually below this threshold. may reveal crystals, mild , and granular casts, further supporting the . In the context of TLS, AUAN is a common renal complication, contributing to in a significant proportion of cases with severe . AUAN integrates with the Cairo-Bishop criteria, which define laboratory TLS by two or more abnormalities from baseline: ≥8 mg/dL (476 μmol/L) or a 25% increase, ≥6.0 mmol/L or 25% increase, ≥4.5 mg/dL (1.45 mmol/L) or 25% increase in adults (≥6.5 mg/dL or 2.1 mmol/L in children), and calcium ≤7.0 mg/dL (1.75 mmol/L) or 25% decrease. Clinical TLS requires laboratory TLS plus renal involvement ( >1.5 times upper limit of normal), cardiac , , or . This framework is particularly relevant as AUAN often arises in TLS. Renal aids in evaluation by demonstrating increased in the due to crystal deposits, without evidence of in cases limited to intratubular obstruction. This finding correlates with severity and helps exclude obstructive uropathy. , though rarely pursued due to procedural risks in AKI, is the gold standard, revealing intratubular crystals—often needle-shaped and birefringent under polarized light—within collecting ducts and distal tubules, confirming pathogenic crystal deposition. Monitoring involves serial assessment of serum creatinine, where an increase of ≥0.3 mg/dL (≥26.5 μmol/L) within 48 hours indicates stage 1 AKI per KDIGO criteria, prompting urgent evaluation for AUAN in at-risk patients.

Differential Diagnosis

Acute uric acid nephropathy (AUAN) must be differentiated from other causes of acute kidney injury (AKI), particularly those involving intratubular obstruction or inflammation, as clinical presentation often overlaps with oliguria, rising serum creatinine, and hyperuricemia. Key differentials include components of tumor lysis syndrome (TLS) such as acute phosphate nephropathy, where calcium phosphate crystals precipitate in tubules, distinguished by markedly elevated serum phosphate levels (>4.5 mg/dL) and absence of urate crystals on urine microscopy, unlike AUAN's characteristic needle-shaped urate crystals. Acute interstitial nephritis (AIN) and contrast-induced nephropathy are also common mimics; AIN features urinary eosinophils and a history of recent drug exposure (e.g., NSAIDs or antibiotics), while contrast nephropathy follows iodinated contrast administration with typically normal uric acid levels and no crystals. Non-TLS conditions further broaden the differential, including , characterized by elevated (>1000 U/L) and on dipstick testing without urate crystals, and (HUS), marked by , schistocytes on peripheral smear, and . Hypercalcemia from or myeloma kidney may present similarly with AKI but shows elevated calcium (>10.5 mg/dL) and light chain , respectively, contrasting AUAN's isolated (>15 mg/dL). The diagnostic algorithm begins by excluding pre-renal (e.g., via low sodium <20 mEq/L and fractional excretion of sodium <1%) and post-renal obstruction (e.g., via renal ultrasound showing hydronephrosis). A urinary uric acid-to-creatinine ratio >1 supports AUAN over other catabolic AKIs, as referenced in diagnostic criteria. Emerging biomarkers like neutrophil gelatinase-associated lipocalin (NGAL) aid in early AKI detection and differentiation from pre-renal causes but lack specificity for AUAN versus other intrinsic renal injuries.

Management

Prevention

Prevention of acute uric acid nephropathy primarily targets high-risk patients undergoing for hematologic malignancies, where (TLS) can precipitate and renal injury. Risk stratification using established TLS scoring systems identifies patients at elevated risk, such as those with , with white blood cell count exceeding 100,000/µL, or bulky disease with high levels, guiding the intensity of preventive measures. Pharmacologic prophylaxis with , a inhibitor, is recommended for intermediate- to high-risk patients with pretreatment levels below 8 mg/dL, typically administered at 300 mg daily for adults (or 100 mg/m² every 8 hours, not exceeding 800 mg/day) starting 24 to 48 hours before to inhibit production. , another inhibitor, may be used as an alternative to in low- to intermediate-risk patients, particularly when is contraindicated or in renal impairment, at doses of 40-80 mg daily. For high-risk cases or established exceeding 8 mg/dL, , a recombinant uricase, is preferred at 0.2 mg/kg intravenously once daily for up to 5 days (or a fixed 3 mg dose for prophylaxis in adults per 2025 guidelines), enzymatically converting to soluble for rapid reduction. Concomitant use of with is generally avoided due to reduced need for ongoing inhibition after breakdown. Aggressive intravenous hydration forms the cornerstone of prevention, with protocols aiming for 2 to 3 L/m² per day initiated 48 hours prior to to achieve urine output greater than 100 mL/m² per hour, thereby diluting urinary and preventing intratubular . alkalinization using to maintain between 7 and 8 has been historically employed to enhance but is no longer routinely recommended in 2025 guidelines due to the risk of and lack of proven benefit over hydration alone. Close monitoring of electrolytes, , and renal function during prophylaxis ensures timely adjustments, particularly in patients with comorbidities like where overhydration must be avoided.

Treatment

The initial management of acute uric acid nephropathy focuses on aggressive intravenous hydration to promote and prevent further crystal precipitation in the renal tubules. Typically, 3 liters per day of isotonic saline is administered to adults, adjusted based on cardiac and renal status, with the goal of achieving a output exceeding 100 mL per hour. If adequate output is not achieved despite hydration, loop such as are initiated at doses of 40-80 mg intravenously to enhance renal and flush uric acid crystals, while monitoring for . Urate-lowering therapy is essential to rapidly reduce serum uric acid levels and mitigate ongoing tubular damage. Rasburicase, a recombinant urate oxidase, is the preferred agent in acute settings, administered at 0.2 mg/kg intravenously daily for up to 5 days, as it enzymatically converts uric acid to allantoin, which is highly soluble and easily excreted. Allopurinol, a xanthine oxidase inhibitor, is an alternative at reduced doses (e.g., 100-200 mg daily, adjusted for renal function) but is avoided in cases of high tumor burden due to the risk of xanthine accumulation leading to xanthinuria and potential nephropathy. Urine alkalinization with is used selectively if urine is below 7, targeting a of 7-8 to enhance solubility, but requires close monitoring for and precipitation. Recent guidelines as of de-emphasize routine alkalinization, particularly when is employed, due to evidence of limited efficacy and increased risks in hyperphosphatemic states. Supportive care includes for patients with refractory , severe , , or unresponsive to conservative measures. or continuous venovenous hemofiltration is indicated, with the choice depending on hemodynamic stability; these modalities effectively remove and correct imbalances. Ongoing monitoring involves daily measurement of serum uric acid levels, with a target below 7 mg/dL to confirm response, alongside electrolytes, renal function, and urine output assessments every 4-6 hours initially. Treatment duration is typically 3-7 days, guided by resolution of hyperuricemia and improvement in renal function.

Prognosis

With prompt treatment, the short-term prognosis for acute uric acid nephropathy is favorable, with 70-90% of patients achieving recovery of renal function. In severe cases, 20-50% require dialysis, but approximately 80% of those patients experience restoration of renal function following intervention. Long-term risks may include progression to , particularly among patients with recurrent or preexisting . Key prognostic factors include early intervention within 24 hours of symptom onset, peak serum levels below 12 mg/dL, and lack of multi-organ involvement from , all of which are associated with improved outcomes. Mortality is less than 5% with modern care protocols, though it rises to 15-20% in elderly patients or those with significant comorbidities. Recent 2025 insights from meta-analyses highlight improved outcomes with therapy, which reduces the need for dialysis by up to 50% in high-risk patients by rapidly lowering levels.

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