Acute Uric Acid Nephropathy - Causes, Symptoms, Diagnosis, and Treatment

Introduction

Acute uric acid nephropathy is also known as acute urate nephropathy. It is a condition caused by high levels of uric acid in the serum as well as in the urine. This excess uric acid gets deposited in the interstitium and the collecting tubules of the kidney affecting kidney function and progressing rapidly to end-stage renal disease. The exact incidence of acute uric acid nephropathy is unknown, and it is reported to be a rare disease. It is reported to be seen in ten percent of patients undergoing chemotherapy and radiotherapy and often seems to be bilateral. The pathological features of acute uric acid nephropathy are reversible with appropriate management measures.

What Is Uric Acid?

Uric acid is a weak organic acid formed as an end product of purine metabolism. It exists in two different forms based on the pH. When the pH is less than 5.5, it is called sparingly soluble undissociated uric acid form. The substantially more soluble form, when the pH is 7.4, is the highly represented form that exists in the physiologic system.

What Is Uric Acid Nephropathy?

Uric acid nephropathy is caused due to the deposition of uric acid crystals in the components of the kidney, leading to partial or complete obstruction. This, in turn, progresses to kidney failure.

What Are the Types of Uric Acid Nephropathy?

It is categorized into three types based on the duration of the disease.

• Acute uric acid nephropathy.

• Chronic uric acid nephropathy.

• Uric acid nephrolithiasis.

What Is Acute Uric Acid Nephropathy?

Acute uric acid nephropathy is a severe condition where there is the precipitation of uric acid crystals in the distal tubules and collecting ducts of the kidney. It is characterized by the presence of acute oliguria or acute renal failure with anuria.

What Is the Etiology of Acute Uric Acid Nephropathy?

It is caused mainly due to two reasons either the overproduction of uric acid or the decreased excretion of uric acid.

Major causes include,

• Malignancies with more cell proliferation such as;

  • Lymphomas.

  • Leukemias.

• Conditions causing more cell destruction such as;

  • Radiotherapy.

  • Chemotherapy.

• Also seen in conditions such as;

  • Acute gout.

  • Polycythemia vera, etc.,

Less frequent causes include:

• Tissue Catabolism Due to Seizures - Uric acid levels are elevated following seizures.

• Lesch-Nyhan Syndrome - This is a genetic condition characterized by the overproduction of uric acid.

• Acute Fanconi-like Syndrome -This is a rare disorder that affects the function of the kidneys, causing excessive excretion of uric acid in the urine.

• Familial Renal Hypouricemia - This is a hereditary disorder affecting kidneys causing increased urate excretion.

What Is the Pathogenesis of Acute Uric Acid Nephropathy?

Uric acid is the sparingly soluble organic acid produced as an end product of purine metabolism. The overproduction or decreased excretion of uric acid due to the above said etiologies would precipitate in the kidneys. This precipitated uric acid becomes insoluble in the acidic environment in the distal nephrons of the kidney as humans lack the enzyme called uricase which dissolves the uric acid. This, in turn, affects the normal physiological function of the kidney, thereby progressing to renal failure.

What Are the Symptoms of Acute Uric Acid Nephropathy?

It usually remains asymptomatic until it progresses to severe kidney disease or renal failure. The symptoms include,

• Oliguria (reduced urine output).

• Nausea.

• Vomiting.

• Seizures.

• Tiredness.

• Hematuria (blood in the urine).

• Painful urination.

• Abdominal pain.

• Anuria (no urine in case of renal failure).

How Is Acute Uric Acid Nephropathy Diagnosed?

1. Blood Examination

Serum investigation in patients with acute uric acid nephropathy would reveal,

• Hyperuricemia - Increased uric acid level in the blood.The plasma or serum concentration of urate levels above 15 mg/dl.

• Increased Creatinine Levels - Rapid increase in serum creatinine as renal failure develops.

2. Urinalysis

• Hyperuricosuria- Increased excretion of uric acid in the urine.

• Uric Acid to Creatinine Ratio - The urine uric acid to creatinine ratio will be greater than one. This helps to differentiate acute uric acid nephropathy from other catabolic forms of acute renal failure as urate levels are elevated in those conditions.

• Uric Acid Crystals- Examination of the affected patient’s urine would reveal the presence of uric acid crystals.

3. Microscopic Examination

Light microscopic examination of the renal tissue would reveal the presence of obstructing uric acid casts in the lumen of the interstitial tubule. A giant cell-like reaction may be noticed in the interstitium due to the presence of monosodium urate monohydrate.

How Is Acute Uric Acid Nephropathy Treated?

The main aim of treatment is to prevent the deposition of uric acid within the kidneys and to promote kidney function. The methods of management include,

• Diuretics - Diuretics such as Furosemide can be given to patients, which increases the urine volume and prevents the deposition of urate crystals in the kidney.

• Sodium Bicarbonate and Acetazolamide - Can be given to increase the urinary pH to seven or high in an attempt to increase uric acid solubility. This method of treatment is called urinary alkalinization.

• Xanthine Oxidase Inhibitors - Allopurinol, an archetypal xanthine oxidase inhibitor, is used in the treatment of gout, which in turn reduces the occurrence of hyperuricemia and hyperuricosuria by reducing the serum urate levels.

• Dialysis - Hemodialysis is indicated in patients with acute uric acid nephropathy to decrease the uric acid load in the kidneys.

The general measures advised for those patients include,

• Adequate fluid intake is necessary as it will help the body continue uric acid excretion and prevent uric acid crystal formation.

• Maintaining a healthy diet.

• Reducing the alcohol intake.

• Physical exercise

• Diet with low purine.

What Is the Prognosis of Acute Uric Acid Nephropathy?

The mortality rate of acute uric acid nephropathy was reported to be 50%, but after the introduction of proper treatment modalities, the prognosis has improved considerably in recent times.

Conclusion

Although the prognosis of acute uric acid nephropathy is good with the aid of treatments such as dialysis, diuresis, and urine alkalinization, prevention is always better than cure; patients undergoing chemotherapy and radiotherapy should take preventive measures to prevent the disease development. The patients should be advised to drink adequate water and take moderate to high doses of allopurinol several days before the start of chemotherapy.