Uric Acid Nephropathy: Differential Diagnoses & Workup

/Home/Complications of Leukemia/Leukemia and Uric Acid Levels/Leukemia and Uric Acid Levels Diagnosis and Tests

Uric Acid Nephropathy: Differential Diagnoses & Workup
Medscape

Author: Mark T Fahlen, MD, Inc
Coauthor(s): Mahendra Agraharkar, MD, MBBS, FACP, President, Space City Associates of Nephrology; Medical Director, Chronic Home Dialysis Unit, DaVita Reliant Dialysis Center and DaVita South Shore Dialysis Center

Updated: Feb 9, 2009

Overview:

Introduction
Background

Uric acid is the relatively water-insoluble end product of purine nucleotide metabolism. It poses a special problem for humans because of its limited solubility, particularly in the acidic environment of the distal nephron of the kidney.1 It is problematic because humans do not possess the enzyme uricase, which converts uric acid into the more soluble compound allantoin. Three forms of kidney disease have been attributed to excess uric acid: acute uric acid nephropathy, chronic urate nephropathy, and uric acid nephrolithiasis. These disorders share the common element of excess uric acid or urate deposition, although the clinical features vary.

Causes

* Most cases of acute uric acid nephropathy occur during treatment for leukemia or lymphoma. Uric acid nephropathy is observed more commonly in persons with an acute leukemia than in persons with a chronic form of the disease. It also has been described in association with other malignancies, such as metastatic breast carcinoma, bronchogenic carcinoma, and disseminated adenocarcinoma.
* Seizures or ischemic states can lead to extensive release of cell metabolites and consequent hyperuricemia.
* Hyperuricemic acute renal failure has also been reported during pregnancy-related preeclampsia12 or eclampsia, as well as in the setting of cyclosporine use and renal transplantation.
* Chronic hyperuricemia and gout are the only causes of chronic urate nephropathy, if it exists as a clinical entity.
* The hereditary enzyme disorder HGRPT deficiency, which leads to overproduction of urate, is an indisputable cause of a chronic urate nephropathy leading to renal insufficiency. Several other rare diseases are in this category, including the following:
o Uric acid nephrolithiasis can be caused by any underlying disorder that causes hyperuricosuria. This includes all of the previously mentioned causes of acute uric acid nephropathy, such as malignancy, hypercatabolic states, and the hereditary enzyme deficiencies.
o Uric acid stones develop in 20% of people with gout.
o Acute diarrheal states may increase urinary uric acid concentration through excessive water loss and dehydration, leading to stone formation.
o Urinary pH also tends to decrease with extracellular volume contraction, and gastrointestinal bicarbonate loss may contribute to the acidic urine, thus promoting stone formation.
o Aspirin and probenecid augment uric acid secretion and may lead to stone formation, especially in people with a purine-rich diet.

Differential Diagnoses
Other Problems to Be Considered

Establishing the diagnosis of acute uric acid nephropathy is sometimes complicated by the variety of nephrotoxic drugs, radiographic studies, and associated clinical problems often observed during the early presentation of malignancies. Dehydration, contrast nephropathy, and acute tubular necrosis caused by nephrotoxic drugs or sepsis-related renal failure must be considered in this high-risk population.

Renal complications associated with malignancies that may result in the sudden cessation of kidney function include hypercalcemia; tumor infiltration of the kidneys, ureter, or bladder; and the monoclonal gammopathies, which may cause a myeloma-type kidney disorder. In addition, chemotherapeutic agents may produce nephropathy with a secondary elevation of urate levels. Other causes of elevated urate levels are preexisting renal failure and drugs, including diuretics, salicylates (<2 g/d), ethambutol, pyrazinamide, vitamin A, cyclosporine, and tacrolimus.

The differential diagnosis for chronic urate nephropathy includes alternative etiologies of chronic renal insufficiency, including diabetes, hypertension, atherosclerotic disease, and primary glomerular diseases. Environmental lead poisoning is another consideration in a patient with hypertension, gout, hyperuricemia, and chronic kidney disease.11

Other metabolic stone diseases can mimic uric acid nephrolithiasis, and hyperuricosuria is a known risk factor for calcium stone formation.

Related eMedicine topics:
Acute Tubular Necrosis [Nephrology]
Acute Tubular Necrosis [Pediatrics: General Medicine]
Lead Nephropathy
Workup
Laboratory Studies

* Hyperuricemia is an important finding; urate levels in the plasma often exceed 15 mg/dL and can peak as high as 50 mg/dL. However, tumor lysis syndrome in the context of normouricemia has been reported.13 Progressive azotemia and hyperphosphatemia are other important findings.
* An increased serum lactate dehydrogenase level is suggestive of a large tumor burden and correlates with risk.
* Urinalysis results are usually bland.
o Uric acid and sodium monourate crystals may be observed.
o Although variable, uric acid levels in the urine may be as high as 150-200 mg/dL.
* A random ratio of urinary uric acid to creatinine higher than 1 is also suggestive of acute uric acid nephropathy.
* A disproportionate elevation in serum uric acid levels also can be a diagnostic clue.
* Elevated serum and urinary uric acid levels correlate with the frequency of nephrolithiasis, and 50% of patients with serum uric acid levels greater than 13 mg/dL or urinary uric acid secretion higher than 1100 mg/d will form stones. Uric acid stones are radiolucent, and the urinary uric acid crystals are reddish-orange. Urate crystals have several forms but tend to be needle-shaped or flat, square plates; both are strongly birefringent.

The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.

Copyright© 1994-2009 by Medscape