Metabolic and Environmental Profiling and Imaging for Kidney Stone Risk

Number: 0392


Aetna considers metabolic and environmental profiling for assessing kidney stone risk experimental and investigational because these studies have not been demonstrated in the peer-reviewed medical literature to improve health outcomes of individuals with kidney stones.

Aetna considers the use of computed tomography (CT) or magnetic resonance imaging (MRI) for urolithiasis screening of asymptomatic persons experimental and investigational because there is a lack of clinical evidence regarding their use for this indication.

Aetna considers the use of calcifying nanoparticles for assessing kidney stone risk experimental and investigational becasue its effectiveness has not been established.

Aetna considers the use of genetic/molecular analysis for assessing kidney stone risk experimental and investigational becasue its effectiveness has not been established.


Nephrolithiasis (also known as urolithiasis, renal calculi, or kidney stones) is exceeded in frequency as a urinary tract disorder only by infections and prostatic disease.  Calcium salts, uric acid, cystine, and struvite are the basic components of most kidney stones in the Western Hemisphere.  Calcium stones constitute more than 70 % of all kidney stones.  It has been suggested that there are metabolic as well as environmental risk factors that render urine more conducive to crystallization, thus resulting in an increase risk of stone formation.  Metabolic and environmental profiling involves studies used to ascertain these risk factors of nephrolithiasis.  These clinical and laboratory tests usually entail measurements of a number of blood and urine parameters, including estimates of urine state of saturation with calcium and uric acid salts, net gastro-intestinal alkali absorption, renal threshold of phosphate and other renal clearances, as well as net acid and total nitrogen excretions.

Although there are published studies on metabolic and environmental profiling, the value of these tests in the management of patients with kidney stones is still questionable.  Additionally, there are factors other than urine composition that may play a role in stone formation.  Furthermore, there is a lack of data to show that metabolic and environmental profiling improves the health outcomes of patients with kidney stones.  Although guidelines on urolithiasis from the European Association of Urology (Tiselius et al, 2006) include metabolic profiling, they state that there is "no absolute consensus that a selective treatment is better than a non-selective treatment for recurrence prevention in idiopathic calcium stone disease", and note that an analysis of data from the literature has suggested only a slight difference in favor of treatment directed towards individual biochemical abnormalities.

The significance of urolithiasis screening is controversial.  In a review on the clinical and cost effectiveness of CT and MRI for selected clinical disorders, the Canadian Agency for Drugs and Technologies in Health (CADTH) reported that no clinical or economic evidence was found on the use of CT and MRI for screening urolithiasis.  CADTH concluded that the use of CT or MRI for this indication should be considered investigational (Murtagh et al, 2006).

Dhar and Denstedt (2009) stated that imaging has an essential role in the diagnosis, management, and follow-up of patients with stone disease.  A variety of imaging modalities are available to urologists, including conventional radiography (KUB), intravenous urography (IVU), ultrasound (US), magnetic resonance urography, and CT scans, each with its advantages and limitations.  Traditionally, IVU was considered the gold standard for diagnosing renal calculi, but this modality has largely been replaced by un-enhanced spiral CT scans at most centers.  Renal US is recommended as the initial imaging modality for suspected renal colic in pregnant women and children, but recent literature suggests that a low-dose CT scan may be safe in pregnancy.  Intra-operative imaging by fluoroscopy or US plays a large part in assisting urologists with the surgical intervention chosen for the individual stone patient.  Post-treatment imaging of stone patients is recommended to ensure complete fragmentation and stone clearance.  Plain radiography is suggested for the follow-up of radiopaque stones, with US and limited IVU reserved for the follow-up of radiolucent stones to minimize cumulative radiation exposure from repeated CT scans.  Patients with asymptomatic calyceal stones who prefer an observational approach should have a yearly KUB to monitor progression of stone burden.

Shiekh and associates (2009) noted that although much has been learned regarding the pathogenesis of kidney stones, the reason(s) why some individuals form stones while others do not remains unclear.  Nanoparticles, which have been observed in geological samples, have also been isolated from biological specimens, including kidney stones.  These nanoparticles have certain properties that are consistent with a novel life form, including in vitro self-replication, and contain lipids, DNA and proteins.  Thus, it has been hypothesized that nanoparticles may represent a type of infective agent that initiates stone formation in some patients.  Despite a large body of suggestive evidence, the true biological nature of these entities has been elusive, and controversy remains as to whether these nano-sized particles are analogous to other recently described unusual and novel microorganisms, or a transmissible, yet inert nanoparticle.  Although unique DNA or RNA has yet to be identified, a proteomic biosignature is beginning to emerge that may allow more definitive clinical investigation.  The authors stated that there is need for additional research to further elucidate the role, if any, of calcifying nanoparticles in the formation of kidney stones.

Sayer (2011) stated that nephrolithiasis may be the manifestation of rare single gene disorders or part of more common idiopathic renal stone-forming diseases.  Molecular genetics has allowed significant progress to be made in the understanding of certain stone-forming conditions.  The molecular defect underlying single gene disorders often contributes to a significant metabolic risk factor for stone formation.  In contrast, idiopathic renal stone formation relates to the interplay of environmental, dietary and genetic factors, with hypercalciuria being the most commonly found metabolic risk factor.  Candidate genes for idiopathic stone formers have been identified using numerous approaches, some of which are outlined here.  Despite this, the genetic basis underlying familial hypercalciuria and calcium stone formation remains elusive.  The molecular basis of other metabolic risk factors such as hyperuricosuria, hyperoxaluria and hypocitraturia is being unraveled and is allowing new insights into renal stone pathogenesis.  The author concluded that the discovery of both rare and common molecular defects leading to renal stones will hopefully increase the understanding of the disease pathogenesis.  Such knowledge will allow screening for genetic defects and the use of specific drug therapies in order to prevent renal stone formation.

Tang et al (2012) stated that the role of vitamin D in kidney stone disease is controversial.  Current evidence is inconsistent and existing studies were limited by small sample populations.  These investigators used the 3rd National Health and Nutrition Examination Survey (NHANES III), a large US population-based cross-sectional study, to determine the independent association between serum 25-hydroxyvitamin D [25(OH)D] concentration and prevalent kidney stone disease in a sample of 16,286 men and women aged 18 years or older.  A prevalent kidney stone was defined as self-report of any previous episode of kidney stones.  Among 16,286 adult participants, 759 subjects reported a history of previous kidney stones.  Concentrations of serum 25(OH)D were not different between stone formers and non-stone formers (mean of 29.28 versus 29.55 ng/ml, p = 0.57).  Higher 25(OH)D concentration was not associated with increased odds ratio (OR) for previous kidney stones [OR = 0.99; 95 % confidence interval (CI): 0.99 to 1.01] after adjustment for age, sex, race, history of hypertension, diabetes, body mass index, diuretic use and serum calcium.  Furthermore, after these researchers divided 25(OH)D concentrations into quartiles, or into groups using clinically significant cut-offs (e.g., 40 and 50 ng/ml), still no significant differences were found in stone formation in group comparisons.  The authors concluded that high serum 25(OH)D concentrations were not associated with prevalent kidney stone disease in NHANES III participants.  They stated that prospective studies are needed to clarify the relationship between vitamin D and kidney stone formation, and whether nutritional vitamin D supplementation will increase risk of stone recurrence.

Nguyen et al (2014) noted that increasing 25(OH)D serum levels can prevent a wide range of diseases.  There is a concern about increasing kidney stone risk with vitamin D supplementation.  These investigators used GrassrootsHealth data to examine the relationship between vitamin D status and kidney stone incidence.  The study included 2,012 participants followed prospectively for a median of 19 months; 13 individuals self-reported kidney stones during the study period.  Multi-variate logistic regression was applied to assess the association between vitamin D status and kidney stones.  These researchers found no statistically significant association between serum 25(OH)D and kidney stones (p = 0.42).  Body mass index was significantly associated with kidney stone risk (OR = 3.5; 95 % CI: 1.1 to 11.3).  The authors concluded that a serum 25(OH)D level of 20 to 100 ng/ml has no significant association with kidney stone incidence.

Dasgupta and colleagues (2014) stated that compound heterozygous and homozygous (comp/hom) mutations in solute carrier family 34, member 3 (SLC34A3), the gene encoding the sodium (Na(+))-dependent phosphate co-transporter 2c (NPT2c), cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a disorder characterized by renal phosphate wasting resulting in hypophosphatemia, correspondingly elevated 1,25(OH)2 vitamin D levels, hypercalciuria, and rickets/osteomalacia.  Similar, albeit less severe, biochemical changes are observed in heterozygous (het) carriers and indistinguishable from those changes encountered in idiopathic hypercalciuria (IH).  These investigators reported a review of clinical and laboratory records of 133 individuals from 27 kindreds, including 5 previously unreported HHRH kindreds and 2 cases with IH, in which known and novel SLC34A3 mutations (c.1357delTTC [p.F453del]; c.G1369A [p.G457S]; c.367delC) were identified.  Individuals with mutations affecting both SLC34A3 alleles had a significantly increased risk of kidney stone formation or medullary nephrocalcinosis, namely 46 % compared with 6 % observed in healthy family members carrying only the wild-type SLC34A3 allele (p = 0.005) or 5.64 % in the general population (p < 0.001).  Renal calcifications were also more frequent in het carriers (16 %; p = 0.003 compared with the general population) and were more likely to occur in comp/hom and het individuals with decreased serum phosphate (OR, 0.75, 95 % CI: 0.59 to 0.96; p = 0.02), decreased tubular reabsorption of phosphate (OR, 0.41; 95 % CI: 0.23 to 0.72; p = 0.002), and increased serum 1,25(OH)2 vitamin D (OR, 1.22; 95 % CI: 1.05 to 1.41; p = 0.008).  The authors concluded that additional studies are needed to examine if these biochemical parameters are independent of genotype and can guide therapy to prevent nephrocalcinosis, nephrolithiasis, and potentially, chronic kidney disease.

Rai et al (2014) examined the fate of indeterminate lesions incidentally found on non-contrast computed tomography (NCCT) for suspected urolithiasis.  These investigators performed a retrospective review of 404 consecutive cases of suspected urolithiasis between May 2010 and April 2011.  Data were collected for patient demographics, presence of calculus disease, and additional urologic or non-urologic pathologies and their clinical relevance.  The indeterminate or suspicious lesions were followed-up and the data were reviewed in September 2012.  In total, 404 patients underwent NCCT for renal colic (mean age of 50 years [range of 13 to 91 years]; 165 females).  Minimum follow-up period was 15 months; 58 patients (14 %) had ureteric, 85 (21 %) had renal, and 39 patients (10 %) had combined ureteric and renal stones.  Non-calculus pathologies were found in 107 patients (26 %).  Sixty patients (15 %) had indeterminate lesions.  Of these patients, 6 required operative intervention, 35 had a benign diagnosis after further imaging and multi-disciplinary team meeting, and 13 remained under surveillance after 1 year.  Indeterminate pulmonary lesions (8 of 16) were the commonest lesions to remain under surveillance.  The authors concluded that NCCT is vital for the diagnosis of urolithiasis with a pick up rate of 45 % and remains the standard of care.  However, with incidental detection of potential malignant lesions, a significant minority will need close monitoring, intervention, or both.  In this study, approximately 1/3 of these lesions either remained under surveillance or had intervention.

An UpToDate review on “Diagnosis and acute management of suspected nephrolithiasis in adults” (Curhan et al, 2015) states that “The diagnosis of nephrolithiasis is initially suspected by the clinical presentation.  Helical non-contrast computerized tomography (CT) or ultrasonography can be used initially to visualize and confirm the presence of a stone …. Radiological tests that are less frequently used include plain X-ray, intravenous pyelography, and magnetic resonance imaging.  Some of these tests are used in the initial diagnosis of nephrolithiasis only if CT is unavailable …. Magnetic resonance imaging is rarely used during the management of stone disease, except in the evaluation of pregnant patients, because this modality is not optimal for identifying stones.  Thus, this modality can be utilized if there is a specific indication to reduce radiation exposure”.

CPT Codes / HCPCS Codes / ICD-10 Codes
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":
ICD-10 codes will become effective as of October 1, 2015 :
Metabolic and environmental profiling for assessment of kidney stone risk:
No specific code
CPT codes not covered for indications listed in the CPB:
72192 Computed tomography, pelvis; without contrast material
72193     with contrast material(s)
72194     without contrast material(s) followed by contrast material(s) and further sections
72195 Magnetic resonance (e.g., proton) imaging, pelvis; without contrast material(s)
72196     with contrast material(s)
72197     without contrast material(s), followed by contrast material(s) and further sequences
Other CPT codes related to this CPB:
82340 Calcium; urine quantitative, timed specimen
82507 Citrate
82570 Creatinine; other source
82615 Cystine and homocystine, urine, qualitative
83890 - 83914 Molecular diagnostics [not covered for analysis of assessing kidney stone risk]
83945 Oxalate
83986 pH, body fluid, except blood
84105 Phosphorus inorganic (phosphate); urine
84540 Urea nitrogen, urine
84545 Urea nitrogen, clearance
84560 Uric acid; other source
ICD-10 codes not covered for indications listed in the CPB:
N20.0 Calculus of kidney
Z87.442 Personal history of urinary calculi

The above policy is based on the following references:
    1. Sutton RA. Causes and prevention of calcium-containing renal calculi. West J Med. 1991;155(3):249-252.
    2. Hobarth K, Hofbauer J. Values of routine analysis and calcium/citrate ration in calcium urolithiasis. Eur Urol. 1991;19(2):165-168.
    3. Hiatt RA, Ettinger B, Caan B, et al. Randomized controlled trial of a low animal protein, high fiber diet in the prevention of recurrent calcium oxalate kidney stones. Am J Epidemiol. 1996;144(1):25-33.
    4. Asplin JR, Lingeman J, Kahnoski R, et al. Metabolic urinary correlates of calcium oxalate dihydrate in renal stones. J Urol. 1998;159(3):664-668.
    5. van Drongelen J, Kiemeney LA, Debruyne FM, de la Rosette JJ. Impact of urometabolic evaluation on prevention of urolithiasis: A retrospective study. Urology. 1998;52(3):384-391.
    6. Trinchieri A, Ostini F, Nespoli R, et al. A prospective study of recurrence rate and risk factors for recurrence after a first renal stone. J Urol. 1999;162(1):27-30.
    7. Marangella M, Vitale C, Bagnis C, et al. Idiopathic calcium nephrolithiasis. Nephron. 1999;81 (Suppl 1):38-44.
    8. Tiselius HG, Ackermann D, Alken P, et al. Guidelines on urolithiasis. Arnhem, The Netherlands: European Association of Urology; 2006.
    9. Murtagh J, Foerster V, Warburton RN, et al. Clinical and cost effectiveness of CT and MRI for selected clinical disorders: Results of two systematic reviews. Technology Overview No. 22. Ottawa, ON: Canadian Agency for Drugs and Technologies in Health (CADTH); August 2006. Available at: Accessed April 24, 2007.
    10. Dhar M, Denstedt JD. Imaging in diagnosis, treatment, and follow-up of stone patients. Adv Chronic Kidney Dis. 2009;16(1):39-47.
    11. Ferrandino MN, Bagrodia A, Pierre SA, et al. Radiation exposure in the acute and short-term management of urolithiasis at 2 academic centers. J Urol. 2009;181(2):668-672; discussion 673.
    12. Shiekh FA, Miller VM, Lieske JC. Do calcifying nanoparticles promote nephrolithiasis? A review of the evidence. Clin Nephrol. 2009;71(1):1-8.
    13. Sayer JA. Renal stone disease. Nephron Physiol. 2011;118(1):35-44.
    14. Tang J, McFann KK, Chonchol MB. Association between serum 25-hydroxyvitamin D and nephrolithiasis: The National Health and Nutrition Examination Survey III, 1988-94. Nephrol Dial Transplant. 2012;27(12):4385-4389.
    15. Nguyen S, Baggerly L, French C, et al. 25-Hydroxyvitamin D in the range of 20 to 100 ng/ml and incidence of kidney stones. Am J Public Health. 2014;104(9):1783-1787.
    16. Dasgupta D, Wee MJ, Reyes M, et al. Mutations in SLC34A3/NPT2c are associated with kidney stones and nephrocalcinosis. J Am Soc Nephrol. 2014;25(10):2366-2375.
    17. Rai BP, Ali A, Raslan M, et al. Fate of indeterminate lesions detected on noncontrast computed tomography scan for suspected urolithiasis: A retrospective cohort study with a minimum follow-up of 15 months. Urology. 2014;84(6):1272-1274.
    18. Curhan GC, Aronson MD, Preminger GM. Diagnosis and acute management of suspected nephrolithiasis in adults. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed February 2015.

You are now leaving the Aetna website.

Links to various non-Aetna sites are provided for your convenience only. Aetna Inc. and its subsidiary companies are not responsible or liable for the content, accuracy, or privacy practices of linked sites, or for products or services described on these sites.

Continue >