Uric acid stones - KHA-CARI Guidelines

1 Page 21 Friday, January 26, 2007 6:33 PM. Blackwell Publishing AsiaMelbourne, AustraliaNEPN ephrology1320-5358 2007 The Authors; Journal compilation 2007 Asian Pacific Society of Nephrology? 200712S12125 MiscellaneousKidney StonesThe CARI Guidelines NEPHROLOGY 2007; 12, S21 S25 uric acid stones Date written: January 2005. Final submission: June 2006. Author: Gavin Becker Guidelines . No recommendations possible based on Level I or II evidence SUGGESTIONS FOR CLINICAL CARE trolled trials involving no such therapy ( allopurinol vs placebo in uric acid stone disease) are unlikely to ever be (Suggestions are based on Level III and IV evidence) performed. In the few randomized trials that have been per- formed, a fall in stone frequency is often seen in the control Diagnosis patients ( stone disease effect'), making interpretation of the uncontrolled trials difficult.

2 uric acid calculi should be detected by non-contrast The epidemiology of childhood stones is less clear. Chil- helical computed tomography, as they are radiolucent on dren are more affected by genetic and anatomical disorders, plain radiograph. and require very specific expertise. Accordingly childhood Ultrasound may be a preferable review technique and stones will not be covered in these Guidelines . helical CT is needed to confirm the absence of stones , if indicated. SEARCH STRATEGY. Treatment Databases searched: 1 Diagnosis of uric acid (urate) stones : Increasing urine pH and volume Database(s) searched: Medline (1966 June Week 1 2004) MeSH terms and/or Recurrence of uric acid calculi can be prevented by in- text words for uric acid stones were combined with MeSH.

3 Creasing urine pH and promotion of large urine volumes. terms and text words for identifying diagnostic studies. 2 Prevention of uric acid (urate) stone growth or recurrence: Xanthine oxidase inhibition Database(s) searched: Medline (1966 June Week 1 2004) MeSH terms and Oral allopurinol to reduce urinary urate excretion is text words for uric acid stones were combined with MeSH. effective in preventing renal stones . terms and text words for the interventions, and then combined with: (i) the Cochrane highly sensitive search BACKGROUND for randomized controlled trials (RCT); and (ii) MeSH. terms and text words for identifying meta-analyses and The construction of Guidelines for management of renal systematic reviews.

4 Stone disease is complicated by several issues. The Cochrane Renal Group Specialised Register of Ran- First, diagnosis is critical to good management, but levels domised Controlled Trials was also searched for trials of of evidence have not been described for diagnostic tests par- interventions for uric acid stones . ticularly when there is no comparative test of 100% sensi- Date of searches: 5 July 2004. tivity and specificity. Second, the disease is managed by a variety of specialties, mainly urology, and hence nephrolo- gists cannot claim to have overarching expertise. Finally, WHAT IS THE EVIDENCE? stone disease is one of the oldest diseases known to man. Many therapies were imbedded in practice before random- No RCT are available that address this issue.

5 Ized prospective trials were cornerstones of clinical research. There are no published levels of evidence for epidemiol- Some therapies are so much part of the routine that con- ogy. Levels of evidence for diagnosis depend on a suitable gold standard, for which none exists in stone disease. There Correspondence: Professor Gavin Becker, Department of Nephrol- are no published RCT to evaluate therapies in uric acid ogy, The Royal melbourne Hospital, victoria, Anstralia, 3050. Email: stone disease. It is thus not possible to produce Guidelines for uric acid stone disease based on level I and II evidence. 2007 The Author Journal compilation 2007 Asian Pacific Society of Nephrology Page 22 Friday, January 26, 2007 6:33 PM.

6 S22 The CARI Guidelines LEVEL III AND IV EVIDENCE Clinical indices Epidemiology Clinical indices are of little use in predicting the presence of uric acid in stones . uric acid comprises the major component of 10 20% of Pak et al. showed that uric acid and mixed uric acid - renal stones . uric acid is the major compound of 17% of calcium oxalate stones more common in patients with stones analysed in South Australia, increasing in frequency chronic diarrhoea syndromes and gouty diathesis, but in in hot weather. Seventy-nine per cent of uric acid stones both conditions more patients had non-urate-containing occur in men, with a peak frequency between 60 and stones (usually calcareous) than urate-containing 65 years of age in both Metabolic indices were equally unreliable.

7 Calcareous stones were more common than uric acid -containing stones Diagnosis in patients with hyperuricosuria. It is commonly stated that approximately 50 60% of uric Radiology acid stone-formers have persistently more acid urine than in normals or calcium stone-formers. Millman et al. reported Containing neither calcium nor sulphur, pure uric acid 22 uric acid stone-formers to have urinary pH of , stones are radiolucent with conventional radiography, compared with in 821 calcium prompting the differential diagnoses of blood clot, tumours, Although statistically significant (P < ), this is hardly fungal balls and detached papillae as well as cystine, xan- clinically useful.

8 Pak et al. reported similar findings in a thine and mucoid matrix calculi. With the advent of com- study defining the stone groups slightly puterized tomography (CT) it rapidly became obvious that uric acid stones were very visible using this technique. Treatment Federle et al. reported that nine non-opaque uric acid calculi had CT attenuation values between 300 and 400 Increasing urine pH and volume Hounsfield units (HU), well above those of the likely dif- ferential Resnick et al. showed that size reduc- The medical management of urate stones using increased tion, as with medical dissolution, could be followed by fluid throughput and oral urinary alkalinizers is mainly based repeat CT on the chemical properties of uric acid rather than con- A major problem was insensitively due to CT slice trolled trials.

9 Location, particularly with 10 mm collimation. Helical CT The most important factor is pH. uric acid is a weak scanners have overcome this problem, even with ureteral acid , with a pKa of around In vitro, at this pH about half calculi, which can be at any level, and quite small. Chu exists in the poorly soluble non-disassociated ( uric acid '). et al. reported that of single ureteral stones of any type seen form, and half as the soluble ionized ( urate') form. As the on helical CT in 215 patients, 47% were not visible on pH rises, the solubility increases. At pH 5 the solubility is scout plain radiography, and of these the four stones larger less than 1 mmol/L (150 mg/L), whereas at pH 7 this rises to than 10 mm were composed of uric acid (two) or xanthine nearly 12 mmol/L (2000 mg/L).

10 Urinary alkalinization thus (two).4 should reduce stone growth/recurrence, and promote stone Nakada et al. studied the role of non-contrast helical CT dissolution. uric acid stone-formers tend to have more acid in predicting stone composition, using 3 5 mm collima- urine (pH ) than normals (pH 6 ) and non-urate After passage or retrieval, 17 predominant (>50%) ,10. uric acid calculi were found to have had Hounsfield mea- The second factor is urine volume. Depending on diet surements of mean 344 152 HU, whereas 82 calcium and metabolic factors, the normal upper limit of daily uric oxalate calculi averaged 652 490 HU (P < ). If mean acid excretion is around mmol/24 h (800 mg/24 h).