Clinical Decision on A Diagnostic Test

Clinical Question In a middle aged man with primary gout and azotemia, can a urine uric acid to creatinine ratio diagnose gouty nephropathy?

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Abstract of Article Spot urine uric acid to creatinine ratio used in the estimation of uric acid excretion in primary gout. Moriwaki YMoriwaki Y, Yamamoto T, Takahashi S, Yamakita J, Tsutsumi Z, Hada T.Yamamoto TTakahashi SYamakita JTsutsumi ZHada T Third Department of Internal Medicine, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo , Japan. J Rheumatol Jun;28(6): OBJECTIVE: Uric acid overexcretion in patients with gout is frequently assessed by the measurement of 24 hour urinary uric acid excretion, which is cumbersome with ambulatory patients, and requires accurate timing and complete collection of the specimen. We assessed whether uric acid to creatinine ratio (Uua/Ucr) in spot urine is useful for the estimation of uric acid overexcretion in patients with gout. METHODS: One hundred thirty male patients with gout and 33 non-gout male control subjects were studied. Early morning urine and/or a portion of 24 h collected urine (24 h urine) were used as spot urine samples. Uric acid overexcreters were defined as those with a 24 h urinary uric acid excretion > or = 1000 mg/day, while uric acid underexcreters were defined as those with uric acid clearance < 6 ml/min. RESULTS: There was a significant relationship between 24 h urinary uric acid excretion and early morning urine Uua/Ucr in patients with gout, while no such relationship was observed in controls. No significant difference in Uua/Ucr was observed between patients with gout and controls, or in Uua/Ucr between gout uric acid overexcreters and underexcreters in early morning urine. A significant difference in this value was observed between the 2 groups in the 24 h urine specimens. Although the diagnostic accuracy of gout uric acid overexcretion was 87.2% using early morning urine and 89.6% using 24 h urine, the sensitivity of gout uric acid overexcretion was only 25.0% when using early morning urine and 25.0% when using 24 h urine, when the cutoff value of Uua/Ucr was 0.63 and 0.64, respectively. CONCLUSION: Uua/Ucr using spot urine, especially early morning urine, is not an accurate indicator of uric acid overexcretion in patients with gout.

Relevance Is the objective of the study relevant to your clinical question? – Yes, indirectly – No gold standard diagnostic test for gouty nephropathy – Rule in gouty nephropathy using urine uric acid to creatinine ratio Kelton, J, Kelley, WN, Holmes, EW. A rapid method for the detection of acute uric acid nephropathy. Arch Intern Med 1978; 138:612 Tarng, DC, Lin HY, et al. Renal Function in Gout Patients. Am J Nephrol 1995;15:31-37.

Relevance Is the objective of the study relevant to your clinical question? – Lin et al showed that pure gout (due to chronic hyperuricemia), especially those exhibiting tophi, can cause renal insufficiency. Evidenced by a lower creatinine clearance in gout patients especially with tophi, which is present in our patient.

Relevance Is the objective of the study relevant to your clinical question? – In 1978, Kelton et al showed the clinical utility of urinary uric acid to creatinine ratio in differentiating uric acid nephropathy from renal failure due to other causes. – This study showed the diagnostic value of urine uric acid to creatinine ratio in assessing renal insufficiency due to uric acid nephropathy versus renal failure due to other causes.

Relevance Is the objective of the study relevant to your clinical question? – Moriwaki et al that explored the clinical utility of a spot urine uric acid to creatinine ratio to estimate uric acid excretion in patients with gout. – Brenner’s Nephrology textbook states that a ratio >1.0, as was also used in Kelton’s study, indicates a strong evidence for urate or gout nephropathy. – As such, to answer the above question, we can say that this study is very much relevant to our clinical question.

Validity Guidelines Was there an independent and blind comparison with a reference standard? – No, it was not stated in the journal if there was blinding done in comparing the test with a reference standard.

Validity Guidelines Did the patient sample include an appropriate spectrum of patients to whom the test will be used? – Yes, the study subjects were composed of 130 male patients with gout and 33 non gout healthy control subjects. – The subjects were classified into underexcreters, normoexcreters, overexcreters and mixed.

Validity Guidelines Was the reference standard done regardless of the result of the diagnostic test being evaluated? – Yes. The 24 hour urine collection was used as a reference standard here. Were the methods for performing the test described in sufficient detail to permit replication? – Yes, the procedure was discussed under methodology with adequate detail.

Validity Guidelines OVERALL, IS THE STUDY VALID? – YES, the study met most of the criteria for a valid study.

What are the results? SensitivitySpecificity Early morning urine hr urine Likelihood ratio (+) Likelihood ratio (-) Early morning urine hr urine

CAT MAKER

41% 20% 70% 35% Lower testing threshold Upper testing threshold Pre-test probability 82% (+) (-) 41% 20% 70% 35% 95% Upper testing threshold Lower testing threshold Pre-test probability (-) (+) Early morning urine 24 hr urine

Can the results help me in caring for my patients? Will the reproducibility of the test result and its interpretation be satisfactory in my setting? – Yes, the procedure was adequately described and the interpretation can be applied to our case. Are the results applicable to my patient? – The patients’ characteristics were not fully described in the article. Mean age = of the patients were diagnosed with gout. Apart from the gout and the age of the patient, no further information can be used to compare with our patient’s basic information.

Will the results change my management? Currently, studies of more sensitive markers are few Our concern now for the patient is to rule in diagnosis of gouty nephropathy. We believe that due to lack of more sensitive markers, a 24 hour Uua/Ucr ratio of >1.0 in renal insufficiency points to a uric acid nephropathy rather than renal failure due to other causes.

Resolution of the problem in the scenario Goal: Rule in gouty nephropathy Moriwaki et al confirms that 24 hr Uua/Ucr is still superior over spot urine Uua/Ucr. If the 24 hr Uua/Ucr ratio turns out to be >1.0, we can confidently say that the renal insufficiency in our patient is due to gout nephropathy.