Scope of the guidelines

These guidelines deal with the metabolic evaluation of kidney stones in adults. Other clinical practice guidelines should guide metabolic evaluation of kidney stones in children.

These guidelines deal with the metabolic evaluation of kidney stones in adults. Other clinical practice guidelines should guide metabolic evaluation of kidney stones in children.

Metabolic evaluation testing is an appropriate indicator of high-quality clinical care. Metabolic evaluation is tailored for people with first-time kidney stones and for people with recurrent or at high-risk of kidney stones and has been demonstrated to be cost-effective in the prevention of kidney stone recurrence (1-3).

Stone analysis

a. We recommend stone analysis for all people with recurrent kidney stones. (Strong recommendation, low certainty of the evidence)

Rationale

Stone analysis identifies the composition of a kidney stone. Stone analysis alongside metabolic evaluation allows the management of kidney stones to be tailored. Studies that have examined various approaches to stone analysis have found no approach has a superior performance.

Importantly, people with lived experience of kidney stones want to know the ‘type’ of their kidney stones to tailor their management and effectively prevent kidney stone recurrence (4). Kidney stone analysis is a low-cost procedure across Australia and Aotearoa New Zealand that should be provided for all people with kidney stones to inform their care.

Evidence to decision framework

Studies have compared the performance of imaging techniques, such as infrared spectroscopy, x-ray diffraction or computed tomography (CT) to each other (5-7) or to chemical analysis (8-11) (Appendix C). The findings from these studies are heterogenous. Studies have indicated that Fourier transform infrared spectroscopy, compared to chemical analysis, was more likely to misclassify kidney stones. However, a single centre with twice-yearly quality control surveys reported that chemical analysis produced >10% error rates for common substances such as uric acid, calcium oxalate, and struvite, while infrared spectroscopy (1-5%) exhibited lower errors rates (11). The studies have found that chemical analysis compared to infrared spectroscopy has high sensitivity and low specificity in detecting major stone components, and a low sensitivity and high specificity in detecting minor stone components (8-10).

The included studies all exhibited limitations in methods or only included data from one study. As a result, the certainty of the evidence has been graded as very low.

An Irish qualitative study (12) identified that participants with kidney stone disease want an improved understanding of the formation of their kidney stone. Participants wanted more information on the cause of their disease and accepted further kidney stone testing through stone analysis to support the prevention of kidney stone recurrence. Similarly, participants in the CARI Guidelines consumer workshops (4) discussed their desire to learn more about their stone type, to tailor the treatment and management options. This was ultimately related to their determination and commitment to being able to actively self-manage their health.

[a participant, when asked about a key kidney stones-related priority]

“The type of kidney stone… there is different management for some different types and that’s quite a big thing that I’ve come across in my care.”

“I think one of the things is, after the surgery, it’s the process of going through and analysing why the stones came about. In my case, it’s only after they did the surgery and took it out, they could actually analyse it as calcium oxalate stones. And the doctor, she’s been very good over the last year, trying to figure out why do the calcium oxalate stones get created, looking at every level which had spiked, and some levels which had spiked two years, a year before the surgery.”

Participants also discussed the importance of having one’s stone type analysed as part of standard care procedures, which was also related to discussions about improving consistency of care.

[a participant sharing they had saved their passed stones] “So the urologist looked at them and went, “Oh, I’ve seen something like that in a textbook. We should actually analyse them.” And if it wasn’t for that, I wouldn’t know that I have this [type of stone], and I wouldn’t have good care now…” 

[a similar experience, post-surgery] “… that’s when they got the sample of that one and realised that I was making two different types of stones…”

The Working Group could not identify any other domains of the PROGRESS Plus checklist (gender/sex, religion, education, and social capital) (13) that this recommendation would impact. Access to testing may have associated out-of-pocket costs but public subsidy covers some of the expenses to individuals.

The Working Group acknowledges that there has been little examination of the cost-effectiveness of stone analysis in the management of stone recurrence (Appendix D). The studies that have evaluated cost have largely examined metabolic evaluation and provided no assessment of stone typing (1-3). However, the Working Group identifies that stone analysis conducted in most tertiary centres in Australia and Aotearoa New Zealand are at low cost. In Australia, the MBS item 66590 which examines calculus analysis costs $30.60 (October 2023) (14). The practicalities of collecting stones for analysis may be a barrier for stone analysis. The hassle for people with kidney stones related to the straining of urine for collection and sending off to laboratory for analysis needs to be discussed to ensure appropriate expectations are set and shared between healthcare provider and patient.

Practice points

  • If the stone type is unknown, stone analysis should always be performed. Repeat stone analysis should be considered for subsequent stone events, especially when there is an unusual pattern of recurrence or the response to the preventative strategy is not as expected

  • Stone composition can change over time or as a consequence of treatment and interventions.

Rationale

Stone analysis identifies the composition of a kidney stone. Stone analysis alongside metabolic evaluation allows the management of kidney stones to be tailored. Studies that have examined various approaches to stone analysis have found no approach has a superior performance. Importantly, people with lived experience of kidney stones want to know the ‘type’ of their kidney stones to tailor their management and effectively prevent kidney stone recurrence (4). Kidney stone analysis is a low-cost procedure across Australia and Aotearoa New Zealand that should be provided for all people with kidney stones to inform their care.

Metabolic evaluation

b. We recommend metabolic evaluation for individuals with kidney stones to direct individualised preventative management following the outlined algorithm: (Strong recommendation, low certainty of the evidence)

All people with kidney stones

  • Review of kidney stone events, relevant medical, occupational, medication and family history contributing to kidney stone risk

  • Initial blood test: bicarbonate, calcium, chloride, creatinine, liver function, parathyroid hormone, phosphate, potassium, sodium, urate, and urea

  • Initial midstream urine: exclude infection, pH

People with recurrent kidney stones or at high-risk of stone formation

  • 24hr urinalysis: calcium, citrate, creatinine, magnesium, oxalate, pH, phosphate, potassium, sodium, urea, uric acid, urine volume

  • Initial midstream urine: Cystine screen if stone type unknown, and other risk factors for cystinuria are evident (stones at a young age or strong family history.

Rationale

Undertaking a metabolic assessment for all people with kidney stones will identify underlying medical conditions such as primary hyperparathyroidism, renal tubular acidosis, recurrent urinary tract infection or cystinuria. Full metabolic assessment will identify the underlying causes of stones in over 90% of people with kidney stones (15). Specific management strategies may be required for these conditions before considering if more comprehensive assessment is indicated. Screening for cystinuria may be dependent on available resources, and targeted screening for people with unknown stone types and risk factors may be considered most appropriate. Historically, metabolic evaluation of people at high-risk of kidney stones has been widely underutilised (16), despite its good correlation in detecting stone composition (17). In people with recurrent kidney stones with more than 0.3 stone events per year, metabolic evaluation to direct medical management has been shown to be the most cost-effective compared to nutrition therapy alone, or surgical treatment in people with recurrent kidney stones (1-3). The studies have considered metabolic evaluation to include urinalysis for calcium, oxalate, creatinine, citrate, sodium, and uric acid. We have expanded the urinalysis tests to include pH, potassium, magnesium, phosphate and urea. 24-hour urine composition analysis provides an assessment of stone promoter and inhibitor constituents, supports assessment of dietary risk factors for stone formation, and provides direction around management and response to intervention. The initial blood test includes uric acid, chloride, and parathyroid hormone. Testing parathyroid hormone in conjunction with same day calcium measurement will determine primary and secondary forms of hyperparathyroidism if suspected.

Evidence to decision framework

 

CARI Guidelines undertook a literature review to identify appropriate studies assessing metabolic evaluation testing in people with kidney stones (Appendix B). While no relevant studies were found that met the criteria for reporting on components of metabolic evaluation, i.e., urinalysis testing, blood uric acid testing, and parathyroid hormone testing, previous studies have identified that urine supersaturation in people with kidney stones is well correlated with kidney stone composition (17). We did identify studies that evaluated the cost-effectiveness of metabolic evaluation, with international survey data from ten countries (1), and decision tree analysis studies (2, 3), which are described in the resource and other considerations section below (Appendix C & Appendix D).

Overall, the certainty of the evidence is low. The methodology of the completed economic evaluations all exhibited limitations. All studies used a third-party payer perspective, whilst the societal perspectives and costs were not included in analyses. Survey data was sourced from medical centres across 10 countries, providing descriptive data and calculations based on assumptions of natural history of kidney stone recurrence (1). The decision-tree analyses used simulated data, with assumptions based on the available literature, and appropriate consideration of random events in sensitivity analyses (2, 3). The studies all exhibited methodological limitations and imprecision concerns, due to the small number of studies included. 

A qualitative study conducted in Ireland, involving people with lived experiences of kidney stones, highlighted the importance of control in the management of kidney stones disease (12), emphasising the need for further understanding of potential causes of stone recurrence in people with kidney stones. The use of metabolic evaluation guides nutrition therapy, which was described as empowering, as it enabled participants to self-manage their disease. The study participants also highlighted the need for further information on the underlying causes of kidney stones, i.e., through metabolic evaluation and testing.

In the CARI Guidelines consumer workshops conducted in Aotearoa New Zealand (4), experiences regarding testing and follow-up were frequently discussed. Whilst they did not specifically discuss the types of tests that they wanted to be undertaken, the focus of the discussions centred around consumers’ desire to receive timely feedback following these tests. Participants reported that they would undertake tests after a specialist appointment but would not receive any feedback or results until their next specialist appointment, typically six to twelve months later. However, they shared that more timely feedback, before their next appointment, would enable them to act and make any changes as needed. Being able to do this was strongly related to their desire to self-manage, actively improve their health, and potentially prevent or minimise the risk of recurrence.

“The tests, you do those, you do the urine test for a couple of days or whatever it is, and then you take it all in, and then six months later, you have a follow-up appointment. And [the clinicians] go, “Oh, did you do those tests?”… [another participant] “It’s frustrating”.

“I was actually waiting for some input… into what’s going on [others affirming]… I’m on Manage My Health, so I see it, but I don’t understand it, I don’t really know [what it means]…”

[regarding communicating test results to patients] “Just a simple letter, two weeks later saying we found this, this, and that. We suggest you cut down on salty foods or whatever, for now. And then we’ll test you again in six months or something…”

The Working Group could not identify any other domains of the PROGRESS Plus checklist (gender/sex, religion, education, and social capital) (13) that this recommendation would impact. Access to testing may have associated out-of-pocket costs but public subsidy covers some of the expenses to individuals.

The international survey conducted in 2002 examined the associated costs of conservative treatment (nutrition therapy), medical management, and metabolic evaluation across ten countries, including Australia (1). The metabolic evaluation included at least two 24-hour urinalyses, assessing calcium, oxalate, creatinine, sodium, citrate, and uric acid. The study found that the costs associated with conservative treatment and management via nutrition therapy alone was the most cost-effective approach for people with kidney stones when kidney stone rates were low (<0.3 stones per year) (1). In management for people with higher rates of kidney stone formation (>0.3 stones per year) nutrition therapy alone costs more due to increased episodes of recurrence (1, 3). In people with recurrent kidney stones with a higher stone recurrence rate (>0.3 stones per year) the inclusion of metabolic evaluation (at least two 24-hour urinalyses) to guide medical management was found to be the most cost-effective approach, under the assumption that all medical management was effective despite the metabolic abnormalities identified (2, 3). Importantly, none of the included studies examined the societal perspective, with out-of-pocket costs for people with kidney stones not considered.

The utility of cystine screening when the stone type is known is unclear particularly in resource limited settings. Parathyroid hormone testing for metabolic evaluation is not a universal practice for all laboratories due to practical issues, such as storing the collected sample on ice. Additionally, not all people with kidney stones will be able to undertake parathyroid testing due to a lack of access to appropriate services.

Practice points

      • Metabolic evaluation guides individualised strategies to prevent kidney stone recurrence.
      • 24-hour urinalysis is recommended for individuals who have recurrent kidney stones, multiple stones, high risk of recurrence, or solitary kidney.

Basic metabolic evaluation

      • Universally required for all individuals with kidney stones.
      • Urine pH should be measured using pH devices rather than dipsticks.

Rationale

The measurement of pH using urine dipsticks is insufficient to guide clinical management of kidney stones. A systematic review found dipsticks to be inaccurate at higher pH values, while many study participants reported the use of handheld pH meters as useful and acceptable. The costs of pH meters were similar in the included studies; hence, given their superior accuracy, may be more cost-effective for the measurement of pH in people with kidney stones (18).

      • Consideration should be given to timing of urine pH measurement, as variation in urine pH occurs throughout the course of the day.

Comprehensive metabolic evaluation

      • 24-hour urine collection identifies metabolic (urinary) risk factors for kidney stone formation (promoters and inhibitors of crystallisation). Laboratories will vary in terms of collection preservatives and processing techniques.
      • Advice is needed to support patients to complete collections correctly to avoid inadequate, under-collected specimens and over-collection. Special consideration is necessary for remote or rural locations, as prompt analysis is required.
      • Usual diet and fluid intake should be consumed during 24-hour urine collection to ensure that nutrition risk factors are accurately identified.
      • The timing for 24-hour urine collections is likely to be influenced by factors such as convenience and patient motivation, and a pragmatic approach is recommended.
      • 24-hour urine collection should be deferred until the acute stone episode has resolved and the patient is in their usual environment to best reflect dietary and lifestyle patterns contributing to stone formation risk.

Rationale

The timing of 24-hour urine collection is a contentious issue, with limited evidence available to provide a strong recommendation. Evidence from Norman et al., 1984 (19) and Hess et al., 1997 (20) suggests that delaying 24-hour urine collection by at least 12 weeks would enable more accurate metabolic evaluation and assessment, as patients would be more likely to have passed their stones by this time. The authors argue that, once patients are stone free, their urinary stone risk parameters return to individual baseline levels, enabling more effective evaluation.

In light of this, a recent study from Guzel et al., 2023 (21) assessed whether urinary risk parameters differed for patients with and without residual stone fragments following retrograde intrarenal surgery. 54 stone free patients (mean age = 46.46 ±16.11 years, mean BMI at baseline = 27.94 ±3.93) and 24 patients with residual stone fragments (mean age = 50.08 ±13.75, mean BMI at baseline = 27.72 ±4.24) performed pre- and post-operative 24-hour urine collections. No significant differences were observed between groups for urine oxalate, calcium, citrate, calcium, uric acid, or albumin, nor for any serum values. Given these results, the researchers recommend against delaying 24-hour urinalysis until all stones have been passed, as this unnecessarily delays the metabolic evaluation process and may reduce patient motivation to complete 24-hour urine collections.

      • Collections should not be delayed for stent removal or other urological procedures.

      • Single 24-hour urine collection for all parameters has cost and practicality benefits; however, performing two 24-hour collections is recommended as this enhances the accuracy and reliability of assessment of risk factors for kidney stone formation.

Suggestions for future research

Real world prospective evaluation of metabolic evaluation and stone analysis in Australia and New Zealand should be undertaken.

David J. Tunnicliffe1,2

Adam Mullan3

Andrew J Mallett4,5,6

Lyn Lloyd7

Ieuan Wickham8

Mia Abdy1,2

Brydee Cashmore1,2

Matthew Jose9,10*

Hicham Hassan11,12*

*Authors have contributed equally as Co-Convenors of the Guideline Working Group.

      1. Sydney School of Public Health, The University of Sydney, Sydney, NSW, Australia
      2. Centre for Kidney Research, The Children’s Hospital at Westmead, Sydney, NSW, Australia
      3. Northland Renal Services, Te Tai Tokerau, Northland, New Zealand
      4. Department of Renal Medicine, Townsville University Hospital, Douglas, Queensland, Australia
      5. College of Medicine and Dentistry, James Cook University, Douglas, Queensland, Australia
      6. Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia
      7. Nutrition and Dietetics, Te Toka Tumai, Auckland, Health New Zealand
      8. Consumer partner
      9. School of Medicine, University of Tasmania, Hobart, Tasmania, Australia
      10. Department of Renal Medicine Royal Hobart Hospital, Hobart, Tasmania, Australia
      11. Graduate School of Medicine, University of Wollongong, Wollongong, NSW, Australia
      12. School of Medicine, Lebanese American University School of Medicine, Beirut, Lebanon

The CARI Kidney Stones Working Group have no relevant conflicts of interests to report.

CARI Guidelines receives funding from the Australian and New Zealand Society of Nephrology, the Australian Living Evidence Collaboration, and the National Health and Medical Research Council Emerging Leadership 1 Investigator grant (APP1197337).

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