Prior Authorization Review Panel MCO Policy Submission

Transcription

1 Prior Authorization Review Panel MCO Policy Submission A separate copy of this form must accompany each policy submitted for review. Policies submitted without this form will not be considered for review. Plan: Aetna Better Health Submission Date: 11/01/2018 Policy Number: 0392 Effective Date: Revision Date: Policy Name: Metabolic and Environmental Profiling and Imaging for Kidney Stone Risk Type of Submission Check all that apply: New Policy* Revised Policy Annual Review No Revisions *All revisions to the policy must be highlighted using track changes throughout the document. Please provide any clarifying information for the policy below: CPB 0392 Metabolic and Environmental Profiling and Imaging for Kidney Stone Risk Policy is new to Aetna Better Health of Pennsylvania. Name of Authorized Individual (Please type or print): Signature of Authorized Individual: Dr. Bernard Lewin, M.D. New 11/01/2018

2 Metabolic and Environmental Profiling and Imaging for Kidney Stone Risk - Medical Cli... Page 1 of 14 --> ( Metabolic and Environmental Profiling and Imaging for Kidney Stone Risk Number: 0392 *Please see amendment for Pennsylvania Medicaid at the end of this CPB. Policy 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. Policy His tory Last Review 08/03/2018 Effective: 03/06/2000 Next Review: 04/11/2019 Aetna considers the use of computed tomography (CT) or Review History 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. Definitions A dditiona l In form at ion Clinical Policy Bulletin Notes

3 Metabolic and Environmental Profiling and Imaging for Kidney Stone Risk - Medical Cli... Page 2 of 14 Aetna considers the use of genetic/molecular analysis for assessing kidney stone risk experimental and investigational becasue its effectiveness has not been established. Background 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

4 Metabolic and Environmental Profiling and Imaging for Kidney Stone Risk - Medical Cli... Page 3 of 14 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. Guidelines from the American College of Physicians (2014) on prevention of kidney stones recommends monotherapy with thiazide diuretics, potassium citrate and allopurinol in patients with active disease in which increased fluid intake fails to reduce the formation of stones. The evidence for this recommendation came primarily from calcium stone formers. According to ACP, although biochemistry and some observational data on stone recurrence suggest that the choice of treatment could be based on the type of metabolic abnormality, evidence from randomized, controlled trials is lacking to correlate the drug of choice and stone type to the prevention of stone recurrence. Most patients have calcium stones, notes ACP, and evidence showed that thiazide diuretics, citrates, and allopurinol all effectively reduced recurrence of this stone type. 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

5 Metabolic and Environmental Profiling and Imaging for Kidney Stone Risk - Medical Cli... Page 4 of 14 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.

6 Metabolic and Environmental Profiling and Imaging for Kidney Stone Risk - Medical Cli... Page 5 of 14 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

7 Metabolic and Environmental Profiling and Imaging for Kidney Stone Risk - Medical Cli... Page 6 of 14 versus 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-

8 Metabolic and Environmental Profiling and Imaging for Kidney Stone Risk - Medical Cli... Page 7 of 14 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 = 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 Data were collected for patient demographics, presence of calculus disease, and additional urologic or non-urologic

9 Metabolic and Environmental Profiling and Imaging for Kidney Stone Risk - Medical Cli... Page 8 of 14 pathologies and their clinical relevance. The indeterminate or suspicious lesions were followed-up and the data were reviewed in September 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.

10 Metabolic and Environmental Profiling and Imaging for Kidney Stone Risk - Medical Cli... Page 9 of 14 Wang and colleagues (2016) stated that many epidemiological studies have been conducted to evaluate the association between serum vitamin D levels and the risk of kidney stone. These investigators summarized the evidence from epidemiological studies. Pertinent studies were identified by a search of PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI) and China Biology Medical literature up to July Standardized mean difference (SMD) was conducted to combine the results. Random-effect model was used. Publication bias was estimated using Egger's regression asymmetry test. A total of 7 articles involving 451 kidney stone cases and 482 controls were included in this meta-analysis. The pooled results suggested that kidney stone patients had a significantly higher serum vitamin D level compared with controls [summary SMD = 0.65, 95 % CI: 0.51 to 0.79, I(2) = 97.0 %]. The associations were also significant both in Europe [SMD = 0.35, 95 % CI: 0.17 to 0.53] and in Asia [SMD = 1.00, 95 % CI: 0.76 to 1.25]. No publication bias was found. The authors concluded that the findings of this analysis indicated that serum vitamin D level in kidney stone patients was significantly higher than that in non-kidney stone controls, both in Europe and Asia populations. This study had several drawbacks: (i) 6 of 7 studies were of case-control design and only 1 study was of randomized controlled trial design, (ii) as a meta-analysis of epidemiologic studies, the authors could not rule out that individual studies may have failed to control for potential confounders, which may introduce bias in an unpredictable direction, (iii) for the subgroups of geographic locations, the associations were significant both in Europe and in Asia between serum vitamin D levels and kidney stone risk. Only 1 study was conducted from United States. Thus, these researchers did not combine the results for other populations. Due to this limitation, the results are applicable to Europe and Asia, but cannot be extended to

11 Metabolic and Environmental Profiling and Imaging for Kidney Stone Risk - Medical... Page 10 of 14 other populations. More studies originating in other countries are needed to investigate the association between serum vitamin D levels and kidney stone risk, and (iv) between-study heterogeneity was high in the pooled analysis, but the heterogeneity was not successfully explained by the subgroup analysis and meta-regression. However, other environment variables, as well as their possible interaction may be potential contributors to this disease-effect unconformity. 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 "+": Code Code Description Metabolic and environmental profiling for assessment of kidney stone risk: No specific code CPT codes not covered for indications listed in the CPB: Computed tomography, pelvis; without contrast material with contrast material(s) without contrast material(s) followed by contrast material(s) and further sections Magnetic resonance (e.g., proton) imaging, pelvis; without contrast material(s) with contrast material(s) without contrast material(s), followed by contrast material(s) and further sequences Other CPT codes related to this CPB: Calcium; urine quantitative, timed specimen

12 Metabolic and Environmental Profiling and Imaging for Kidney Stone Risk - Medical... Page 11 of 14 Code Code Description Citrate Creatinine; other source Cystine and homocystine, urine, qualitative Oxalate ph, body fluid, except blood Phosphorus inorganic (phosphate); urine Urea nitrogen, urine Urea nitrogen, clearance Uric acid; other source ICD-10 codes not covered for indications listed in the CPB: N20.0 Calculus of kidney Z Personal history of urinary calculi The above policy is based on the following references: 1. Sutton RA. Causes and prevention of calciumcontaining renal calculi. West J Med. 1991;155(3): Hobarth K, Hofbauer J. Values of routine analysis and calcium/citrate ration in calcium urolithiasis. Eur Urol. 1991;19(2): 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.

13 Metabolic and Environmental Profiling and Imaging for Kidney Stone Risk - Medical... Page 12 of Asplin JR, Lingeman J, Kahnoski R, et al. Metabolic urinary correlates of calcium oxalate dihydrate in renal stones. J Urol. 1998;159(3): 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): 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): Marangella M, Vitale C, Bagnis C, et al. Idiopathic calcium nephrolithiasis. Nephron. 1999;81 (Suppl 1): Tiselius HG, Ackermann D, Alken P, et al. Guidelines on urolithiasis. Arnhem, The Netherlands: European Association of Urology; 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 Available at: Accessed April 24, Dhar M, Denstedt JD. Imaging in diagnosis, treatment, and follow-up of stone patients. Adv Chronic Kidney Dis. 2009;16(1): 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): ; discussion Shiekh FA, Miller VM, Lieske JC. Do calcifying nanoparticles promote nephrolithiasis? A review of the evidence. Clin Nephrol. 2009;71(1): Sayer JA. Renal stone disease. Nephron Physiol. 2011;118(1):35-44.

14 Metabolic and Environmental Profiling and Imaging for Kidney Stone Risk - Medical... Page 13 of Tang J, McFann KK, Chonchol MB. Association between serum 25-hydroxyvitamin D and nephrolithiasis: The National Health and Nutrition Examination Survey III, Nephrol Dial Transplant. 2012;27(12): 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): 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): 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): Curhan GC, Aronson MD, Preminger GM. Diagnosis and acute management of suspected nephrolithiasis in adults. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed February American College of Physicians (ACP). Dietary and pharmacologic management to prevent recurrent nephrolithiasis in adults: A clinical practice guideline from the American College of Physicians. Ann Intern Med. 2014;161(9): Wang H, Man L, Li G, et al. Association between serum vitamin D levels and the risk of kidney stone: Evidence from a meta-analysis. Nutr J. 2016;15: Wong Y, Cook P, Roderick P, Somani BK. Metabolic syndrome and kidney stone disease: A systematic review of literature. J Endourol. 2016;30(3):

15 Metabolic and Environmental Profiling and Imaging for Kidney Stone Risk - Medical... Page 14 of 14 Copyright Aetna Inc. All rights reserved. Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change. Copyright Aetna Inc.

16 AETNA BETTER HEALTH OF PENNSYLVANIA Amendment to Aetna Clinical Policy Bulletin Number: 0392 Metabolic and Environmental Profiling and Imaging for Kidney Stone Risk There are no amendments for Medicaid. New 11/01/2018