Hyperuricaemic nephropathy (gout, purines and interstitial nephritis)

• What is hyperuricaemic nephropathy (gout, purines and interstitial nephritis)?
• Statistics on hyperuricaemic nephropathy
• Risk factors for hyperuricaemic nephropathy
• Progression of hyperuricaemic nephropathy
• Symptoms of hyperuricaemic nephropathy
• Clinical examination of hyperuricaemic nephropathy
• How is hyperuricaemic nephropathy diagnosed?
• How is hyperuricaemic nephropathy treated?
• References

What is hyperuricaemic nephropathy (gout, purines and interstitial nephritis)?

Hyperuricaemic nephropathy is a disease of the kidneys.

There are three forms of renal disease associated with hyperuricaemia:

1. Chronic hyperuricaemic nephropathy;
2. Acute hyperuricaemic nephropathy;
3. Uric acid stone formation: Nephrolithiasis (see Urinary Stone Disease).

Statistics on hyperuricaemic nephropathy

The prevalence of hyperuricaemia in Europe and the USA is approximately 5%.

The presence of hyperuricaemia increases a patient’s risk of developing gouty arthritis and crystal nephropathy. The exact risk of developing either of these conditions in the presence of elevated uric acid levels cannot be given as an absolute risk as hyperuricaemia can occur with varying severity.

Risk factors for hyperuricaemic nephropathy

The central risk factor for the development of hyperuricaemic nephropathy is raised serum uric acid levels, or hyperuricaemia. Uric acid is the final breakdown product of purines within the body.

Uric acid levels rise in the body as a result of either:

• Increased production; or
• Decreased excretion.

Increased production of uric acid

• Enzyme defects:
  • HGPRT (hypoxanthine-guanine-phosphoribosyl transferase) deficiency;
  • Phosphoribosyl-pyrophosphate overactivity;
  • Glucose-6-phosphate deficiency.
• Increased purine turnover:
  • Myeloproliferative disorders (polycythaemia vera);
  • Lymphoproliferative disorders (leukaemia);
  • Certain forms of cancer.
• Increased consumption in diet of offal, oily fish, and beer.

Impaired excretion of uric acid

• Chronic renal disease;
• Drugs therapy especially thiazide diuretics and aspirin;
• Hypertension;
• Hypothyroidism;
• Hyperparathyroidism;
• Increased lactic acid production from excessive exercise, alcohol or starvation.

Progression of hyperuricaemic nephropathy

Chronic hyperuricaemic nephropathy

The occurs in patients with a less severe but more protracted state of hyperuricaemia. The condition usually arises subtle, with an insidious decline of renal function that may progress to renal failure over many years.

Acute hyperuricaemic nephropathy

This form of disease occurs mosst frequently in patient undergoing chemotherapy, in which cells are destroyed releasing large amounts of purine which is then metabolised to uric acid. The onset of symptoms is abrupt, resulting in oliguric renal failure over a short period. With appropriate therapy, the patient can be supported through their acute renal failure while uric acid levels are controlled with agents such as allopurinol.

How is hyperuricaemic nephropathy diagnosed?

1. Establish baseline renal function:
   • Bloods;
   • Urea, electrolytes and creatinine;
   • Serum uric acid.
2. Investigate for obstruction:
   • Intravenous pyelogram;
   • Renal ultrasonography.

How is hyperuricaemic nephropathy treated?

1. Reduce uric acid concentration: Start treatment with allopurinol immediately;
2. Alkalinise urine: Give IV 1.26% sodium bicarbonate with acetazolamide (500mg PO stat, then 250mg tds);
3. Monitor urea, creatinine and electrolytes and support through acute acute renal failure if present. Consider dialysis if renal failure cannot be controlled by conservative means. Expect recovery in 7-21 days.
4. Consider percutaneous nephrostomy if extrarenal obstruction exists and patient in complete ureteric obstruction. Stones may then pass spontaneously or be removed by urological surgeon.

References

1. Braunwald, Fauci, Kasper, Hauser, Longo, Jameson. Harrison’s Principles of Internal Medicine. 15th Edition. McGraw-Hill. 2001.
2. Cotran, Kumar, Collins 6th edition. Robbins Pathologic Basis of Disease. WB Saunders Company. 1999.
3. Kumar P, Clark M. CLINICAL MEDICINE. WB Saunders 2002 Pg 545-549.
4. Longmore M, Wilkinson I, Torok E. OXFORD HANDBOOK OF CLINICAL MEDICINE. Oxford Universtiy Press. 2001.