Uric Acid Nephropathy - Types, Etiology, Diagnosis and Treatment

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 in the physiologic system.

What Is Uric Acid Nephropathy?

Uric acid nephropathy is characterized by the deposition of urate crystals in the kidney, causing partial or complete obstruction, thereby leading to kidney failure.

What Is the Pathogenesis of Uric Acid Nephropathy?

Uric acid is the sparingly soluble organic acid produced as an end product of purine metabolism. The overproduced uric acid or the partially excreted 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. The uric acid will get deposited in the renal medulla, causing precipitation of the urate crystalsin the kidney. This results in the formation of characteristic tophus (the deposition of uric acid crystals in the kidney). The tophus promotes inflammation of the organelles, followed by fibrosis and subsequent loss of nephrons. Deteriorating the kidney function and progressing to end-stage renal disease.

What Are the Types of Uric Acid Nephropathy?

It is classified into three types which include -

1. Acute Uric Acid Nephropathy - Acute uric acid nephropathy is a severe condition with the precipitation of uric acid crystals in the distal tubules and collecting ducts of the kidney. It is characterized by acute oliguria or acute renal failure with anuria.

2. Chronic Uric Acid Nephropathy - Chronic uric acid nephropathy, also known as gouty nephropathy, is characterized by the deposition of monosodium urate crystals in the renal parenchyma and the collecting ducts of the kidney. This, in turn, affects renal function increasing the serum urate levels and tophus formation in the skin, cartilage, bone, and joints.

3. Uric Acid Nephrolithiasis - Uric acid nephrolithiasis is the formation of urinary stones associated with systemic conditions such as diabetes mellitus, obesity, hypertension, and metabolic syndromes. It is mainly caused due to the decreased urinary pH in conditions causing precipitation of the urate crystals and the formation of uric acid stones.

What Is the Etiology of Uric Acid Nephropathy?

1. Acute Uric Acid Nephropathy - Is mainly caused due to the overproduction as well as over-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.

Less frequent causes include:

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

• Lesch-Nyhan Syndrome - It is a genetic syndrome 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.

2. Chronic Uric Acid Nephropathy - It is mainly caused due to the following condition -

• Gout - It is a form of arthritis characterized by pain and inflammation of the joints due to the deposition of urate crystals in the joint tissues. These excessive uric acid synthesized in the body get deposited in the kidneys, progressing to chronic uric acid nephropathy and renal failure.

3. Uric Acid Nephrolithiasis

The common causes which may increase the serum urate levels, thereby leading to the deposition of urate crystals and formation of urate stones in the kidney, include -

• Diabetes mellitus (increased blood sugar levels).

• Hypertension (increased blood pressure levels).

• Metabolic syndromes (syndromes that affect the normal body metabolism).

• Obesity (increased body weight).

Risk factors include -

• Old age.

• Hot and dry climatic conditions.

• Low urine pH.

• Decreased urine volume.

What Are the Signs and Symptoms of Uric Acid Nephropathy?

1. Acute Uric Acid Nephropathy- Remains asymptomatic until it progresses to evolving 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).

2. Chronic Uric Acid Nephropathy - It is often associated with gout, and the symptoms include -

• Nausea.

• Vomiting.

• Lethargy.

• Joint pain.

• Oliguria (reduced urine output).

• Hematuria (blood in the urine).

3. Uric Acid Nephrolithiasis - The symptoms of uric acid stones causing the blockage in the urinary drainage pathway include -

• Pain in the loin or back region.

• Nausea.

• Vomiting.

• Fever.

• Chills.

• Foul-smelling urine

• Cloudy urine.

• Hematuria (blood in the urine).

How Is Uric Acid Nephropathy Diagnosed?

Diagnostic methods include -

1. Blood Examination

Serum investigation of uric acid nephropathies would reveal -

• Hyperuricemia - Increased uric acid level in the blood. The plasma or serum concentration of urate levels above 15 mg/dl (milligrams per deciliter). Hyperuricemia is a common finding in all three types of uric acid nephropathies.

• Increased Creatinine Levels - Rapid increase in serum creatinine as renal failure develops. It is the main finding in acute uric acid nephropathy.

• Hypercalcemia- Increased blood calcium levels and hyperuricemia may indicate uric acid nephrolithiasis.

2. Urine Examination

• Hyperuricosuria - Increased excretion of uric acid in the urine. It is observed in all three types.

• 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 in all three types of uric acid nephropathies.

• Urinary pH - Patients exhibiting low urinary pH, less than 5.5, indicate the presence of urate stones.

3. Ultrasound of Kidney

• It helps to find out the urate stones, their size, and placement.

4. Computed Tomography (CT) Scans

• Gives a detailed picture of urate stone size, position, and thickness.

5. 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. In addition, a giant cell-like reaction may be noticed in the interstitium due to the presence of monosodium urate monohydrate.

How Is Uric Acid Nephropathy Treated?

The main aim of treatment in all three types 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 with acute and chronic uric acid nephropathies, increasing the urine volume and preventing urate crystals deposition in the kidney.

• Sodium Bicarbonate and Acetazolamide - Can be given to patients with acute and chronic uric acid nephropathies to increase the urinary pH to 7 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 lowers the occurrence of hyperuricemia and hyperuricosuria by decreasing the serum urate levels.

• Colchicine and NSAIDs - Can be given to patients with gouty nephropathy to relieve the symptoms such as pain and inflammation of the joints.

• Shock Wave Lithotripsy - In the case of large uric acid stones, this procedure is used to break the stones and eliminate them in the urine. It uses high-energy sound waves to break the urate stones.

• Ureteroscopy - In this method, an endoscopic tube is inserted into the ureter to reach the stones in the kidney and remove them.

• Percutaneous Nephrolithotomy - In this method, a small hole is put in the back region to reach the kidneys, and the stone is removed surgically.

• Dialysis - Hemodialysis is indicated in patients with high uric acid load in the blood and the kidneys. This helps in decreasing the uric acid load.

The general measures advised for patients with uric acid nephropathies include -

• Adequate fluid intake is necessary as it will help the body continue uric acid excretion and prevent uric acid crystal formation. In addition, adequate water intake will help eliminate the small uric acid stones through urine.

• Maintaining a healthy diet.

• Reducing alcohol intake.

• Physical exercise

• Diet with low purine.

What Is the Prognosis of Uric Acid Nephropathy?

The prognosis of all three types of uric acid nephropathies is reported to be good with timely treatment. However, acute and chronic uric acid nephropathies would result in renal failure more rapidly than uric acid nephrolithiasis if not treated promptly.

Conclusion

Uric acid metabolism and its physiological maintenance play a significant role in kidney function. Any form of disturbance in this would result in damage to the kidney tissues, thereby affecting its function. Therefore, proper education about these entities among patients with susceptible conditions such as malignancies, systemic diseases, and hereditary conditions is necessary to prevent the advent of kidney failure.