UCSF UC San Francisco Previously Published Works

Title The Role of the 24-Hour Urine Collection in the Prevention of Kidney Stone Recurrence.

Permalink https://escholarship.org/uc/item/8vc0s2g1

Journal The Journal of urology, 197(4)

ISSN 0022-5347

Authors Hsi, Ryan S Sanford, Thomas Goldfarb, David S et al.

Publication Date 2017-04-01

DOI 10.1016/j.juro.2016.10.052

Peer reviewed

eScholarship.org Powered by the California Digital Library University of California 1 58 2 59 3 60 4 61 5 62 6 63 7 The Role of the 24-Hour Urine Collection in the Prevention 64 8 of Kidney Stone Recurrence 65 9 66 10 Ryan S. Hsi,* Thomas Sanford, David S. Goldfarb and Marshall L. Stoller 67 11 68 From the Department of Urologic Surgery, Vanderbilt University School of Medicine (RSH), Nashville, Tennessee, 12 Department of Urology, University of California-San Francisco (RSH, TS, MLS), San Francisco, California, and Nephrology 69 13 Section, New York Harbor Veterans Affairs Healthcare System and New York University Langone Medical Center, 70 14 New York University School of Medicine (DSG), New York, New York 71 15 Accepted for publication October 2, 2016. 72 16 Purpose: Kidney stone prevention relies on the 24-hour urine collection to No direct or indirect commercial incentive 73 17 diagnose metabolic abnormalities and direct dietary and pharmacological ther- associated with publishing this article. 74 apy. While its use is guideline supported for high risk and interested patients, The corresponding author certifies that, when 18 applicable, a statement(s) has been included in 75 19 evidence that the test can accurately predict recurrence or treatment response is the manuscript documenting institutional review 76 20 limited. We sought to critically reassess the role of the 24-hour urine collection in board, ethics committee or ethical review board 77 stone prevention. study approval; principles of Helsinki Declaration 21 were followed in lieu of formal ethics committee 78 22 Materials and Methods: In addition to a MEDLINEÒ search to identify approval; institutional animal care and use 79 23 controlled studies of dietary and pharmacological interventions, evidence sup- committee approval; all human subjects provided 80 written informed consent with guarantees of 24 porting the AUA (American Urological Association) and EAU (European Asso- confidentiality; IRB approved protocol number; 81 25 ciation of Urology) guidelines for metabolic stone prevention were evaluated. animal approved project number. 82 26 Additionally, the placebo arms of these studies were examined to assess the stone * Correspondence: Department of Urologic 83 Surgery, Vanderbilt University Medical Center, 27 clinic effect, that is the impact of regular office visits without specific treatment A-1302 Medical Center North, Nashville, 84 28 on stone recurrence. Tennessee 37232 (e-mail: [email protected]). 85 29 Results: The 24-hour urine test has several limitations, including the complexity Editor’s Note: This article is the 86 30 of interpretation, the need for repeat collections, the inability to predict stone of 5 published in this issue for 87 31 recurrence with individual parameters and supersaturation values, the unclear which category 1 CME credits 88 can be earned. Instructions for 32 rationale of laboratory cutoff values and the difficulty of determining collection obtaining credits are given with 89 33 adequacy. Only 1 prospective trial has compared selective dietary recommen- the questions on pages and 90 34 dations based on 24-hour urine collection results vs general dietary instructions. . 91 35 While the trial supported the intervention arm, significant limitations to 92 36 the study were found. Placebo arms of intervention trials have noted a 0% to 93 37 61% decrease in stone recurrence rate and a remission rate during the study of 94 38 20% to 86%. 95 39 Conclusions: Whether all recurrent stone formers benefit from 24-hour urine 96 40 collection has not been established. Additional comparative effectiveness trials 97 41 are needed to determine which stone former benefits from selective therapy, as 98 42 guided by the 24-hour urine collection. 99 43 100 44 Key Words: kidney, urolithiasis, secondary prevention, 101 45 urine specimen collection, recurrence 102 46 103 47 104 48 105 49 THE goal of metabolic management recommended that a 24-hour urine 106 50 for kidney stones is to prevent recur- collection should represent the spe- 107 51 rent stone episodes, which occur in up cific metabolic evaluation to be per- 108 52 to 50% of individuals after 10 years.1 formed in high risk stone formers.2,3 109 53 National guideline panels have The rationale for testing is that 110 54 111 55 0022-5347/17/1974-0001/0 http://dx.doi.org/10.1016/j.juro.2016.10.052 112 THE JOURNAL OF UROLOGY® Vol. 197, 1-6, April 2017 56 www.jurology.com j 1 113 57 Ó 2017 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH,INC. Printed in U.S.A. 114

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115 identifying specific metabolic abnormalities in urine the dietary prevention of stone recurrence. In a 172 116 would enable the clinician to make individualized study by Kocvara et al, 242 idiopathic calcium 173 117 diet and pharmacological interventions to correct based, first-time stone formers were evenly assigned 174 118 these abnormalities and reduce the recurrence risk. to a group with a specific dietary regimen tailored 175 119 There is weighty reliance on this test to guide the by a 24-hour urine collection or to a second group in 176 120 metabolic stone management. According to AHRQ which general, nonselective dietary measures were 177 121 (Agency for Healthcare Research and Quality), begun.7 After 3 years, stone recurrence and/or 178 122 additional studies are needed “to estimate the growth occurred in 7% of the intervention group and 179 123 effectiveness, cost-effectiveness and harms of in 23% of the nonselective group (p <0.01). 180 124 different kidney stone evaluation, treatment and While these results would appear to favor the 181 125 followup strategies vs a control strategy to prevent 24-hour urine collection, several issues should be 182 126 stone recurrence.”4 Which stone formers should noted. The intervention group had regular follow- 183 127 undergo this test, when and how often is unclear. ups, including repeat collections and dietary 184 128 We examine the evidence supporting the role of the adjustment, while the nonselective group had no 185 129 24-hour urine collection for the prevention of future followup. Urine collections were performed only in 186 130 stone events. the intervention group and, except for an improve- 187 131 ment in uricosuria, there was no appreciable 188 132 improvement in any other urinary parameters. In 189 133 ROLE IN CONTEMPORARY PRACTICE fact, there were significantly higher mean levels of 190 134 Both AUA and EAU guidelines recommend 24-hour urinary calcium and oxalate at the end of the study 191 2,3 135 urine collections in the high risk individual. AUA compared to baseline in the selective therapy group. 192 136 also recommends testing in the motivated first-time The difference in stone recurrence rates in the 2 193 137 stone former. In the EAU guidelines, 2 consecutive groups may be explained more by the stone clinic 194 138 collections are recommended initially, again after effect, which has been documented to have a sig- 195 139 initiating dietary or pharmacological prevention for nificant effect on recurrence.8 196 3 140 8 to 12 weeks and every 12 months thereafter. AUA 197 141 recommends 1 or 2 collections performed initially, Drawbacks 198 142 an additional collection within 6 months of inter- No laboratory test is perfect but the interpretation 199 143 vention to assess adherence and response, and of the 24-hour urine collection has several issues 200 2 144 yearly collection thereafter. (see Appendix). Often more than 1 abnormality is 201 145 The utilization of the collection is increasingly present, placing the clinician in a quandary about 202 146 viewed as a quality metric in nephrolithiasis care. which abnormality to address. Borderline values 203 147 In current practice, however, this test is uncom- may have clinical importance. Stone composition 204 148 monly performed. Among privately insured Ameri- provides value in the role of medical management, 205 149 cans identified as high risk for stone recurrence, the especially if the composition is uric acid or cystine, 206 5 150 prevalence of testing is only 7%. Of those tested, for example. However, it is less helpful for the pre- 207 151 16% with an abnormality in the initial collection dominant calcium oxalate stone former in whom a 208 6 152 undergo repeat collections within 6 months. Why 24-hour urine collection is performed. 209 153 overall use is so low is unclear but before broad The 24-hour urine collection negates diurnal and 210 154 quality metrics tied to reimbursement are imple- nocturnal variations in the urinary constituents 211 155 mented, more study is needed to determine who related to diet and metabolism, so that often a single 212 156 benefits most from this test. test is difficult to interpret. While performing 1 or 2 213 157 consecutive collections as part of the initial workup 214 158 has been debated, variation is intrinsic to patient 215 24-HOUR URINE COLLECTION 159 diets and activities, so that it remains uncertain 216 160 Rationale whether doing more collections and making more 217 161 A systemic search was done in PubMedÒ for orig- diagnoses increases clinical value. Patients may 218 162 inal publications involving adult kidney stone dis- prefer to do collections at home, on the weekends, 219 163 ease formers up to 2016. The search terms included while having different dietary habits during the 220 164 were kidney stones, urolithiasis, nephrolithiasis, week, or while at work or school, leading to further 221 165 medical management, prevention, 24-hour urine, confusing variation. 222 166 Litholink and randomized clinical trial. We The 24-hour urine collection is limited in its 223 167 reviewed relevant systemic reviews and clinical ability to predict recurrence and prognosticate risk. 224 168 guidelines for studies relating to the usefulness of The definition of stone recurrence based on symp- 225 169 the 24-hour urine collection. toms and/or radiographic findings has varied among 226 170 To date, there has been only 1 prospective trial different trials, which this contributes to the diffi- 227 171 evaluating the role of the 24-hour urine collection in culty of relating 24-hour urine results to specific 228

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229 clinical end points. Among randomized controlled dietary regimens when performing the collections, in 286 230 diet and pharmacological trials, baseline urinary a gamesmanship that leads to further limits to the 287 231 calcium, oxalate and citrate do not predict recur- interpretation of results. 288 232 rence outcomes.9 Some positive trials of citrate did The relationship between individual 24-hour 289 233 not require the intervention group to have hypoci- urinary abnormalities is poorly understood and 290 234 truria.10,11 In other words, citrate supplementation undermines our understanding of how to interpret 291 235 helps recurrent stone formers with normal range the test. The best example of this is the relationship 292 236 baseline urinary citrate. The same is true for of urinary citrate and pH in response to citrate 293 237 several thiazide trials, which did not require supplementation. Urinary citrate inhibits calcium 294 238 hypercalciuria as an inclusion criterion.12,13 The stone formation but also leads to bicarbonaturia and 295 239 only positive dietary intervention trial, that by urinary alkalinization. That latter effect is used 296 240 Borghi et al, did not require more than hyper- successfully in the prevention of uric acid and 297 241 calciuria among eligible participants.14 Further- cystine stones. However, some patients taking 298 242 more, the rates of metabolic abnormalities were citrate supplements have more citruria and others 299 243 similar among single stone formers compared to have more alkalinization. For example, in a study of 300 244 recurrent stone formers.15,16 Therefore, additional 572 patients, the correlation between urinary cit- 301 245 study is needed to further refine the analysis of rate and pH was poor (r ¼0.04, p ¼ 0.36) and the 302 246 urinary risk factors to predict stone recurrence. finding persisted when controlled for age, gender, 303 247 Stone formers can have normal 24-hour urine body weight, urinary volume and thiazide use.23 304 248 collections and nonstone formers can have abnormal These findings suggest that additional factors 305 249 collections, raising the question of whether current beyond citrate supplementation and excretion in- 306 250 laboratory cutoff parameters are appropriate. In a fluence urinary pH and interpretation of the results 307 251 study of 5,942 geriatric (age greater than 65 years) must take into account the complexity of the mul- 308 252 stone formers, the rate of finding no metabolic tiple, distinctly measured values. 309 253 abnormalities was more than 35%.17 In a separate It is unclear how to utilize calculated urinary su- 310 254 analysis of 1,392 stone formers, after excluding low persaturation indexes in the 24-hour urine report. It 311 255 urine volume in 23% and infection in 2.5% as causes has been shown that these supersaturation indexes 312 256 for stone formation, 1.1% had no metabolic abnor- correlate closely with stone type24 and this analysis 313 257 mality identified.18 Curhan et al found that specif- has been advocated as a method to inform future 314 258 ically among nonstone formers, the rates of stone risk and monitor treatment.2 However, in these 315 259 hypercalciuria, hyperoxaluria, hyperuricosuria, studies individual supersaturation indexes were 316 260 hypocitruria and low urine volume were 14% to compared in isolation with stone type and not with 317 261 27%, 7% to 43%, 8% to 40%, 3% to 9% and 7% to 20% the combination of multiple urinary values on the 318 262 among 3 prospective cohorts of health professionals, report, which often can have multiple abnormal 319 263 respectively.19 As they noted, the cut points for values. Moreira et al studied 503 stone formers using 320 264 abnormal values are arbitrary with no rational stone composition data.25 While univariate compar- 321 265 basis for men and women to have different thresh- isons of supersaturation and stone types showed 322 266 olds for the definition of hypercalciuria. Whether strong associations, a multivariate model correctly 323 267 different cutoffs for defining urinary abnormalities predicted stone type in only 64% of cases. Additional 324 268 should be used among different ethnic groups has study is needed on how to interpret urinary super- 325 269 also been debated.20 saturation indexes in the context of the other 326 270 The adequacy of the 24-hour urine collection, measured and calculated urinary parameters. 327 271 judged by the urinary creatinine-to-body weight In addition, to our knowledge the degree to which 328 272 ratio, is an imprecise measure. Generally, reference reducing supersaturation for calcium stones is 329 273 ranges of 15 to 20 mg/kg for women and 18 to 24 mg/kg necessary to prevent new stones has not been tested 330 274 for men are used to determine collection complete- in carefully controlled trials. A rule of thumb to 331 275 ness. In a study of 381 initial collections, 51% were decrease calcium oxalate supersaturation by 50% 332 276 outside the reference range, 37% of patients had an is not rigorously evidence-based. It is worth 333 277 “undercollection” and 14% had an “overcollection.”21 noting that the effect of citrate supplementation to 334 278 In a separate study of 1,502 patients with 24 or prevent calcium stones is in part attributed to 335 279 48-hour collections, 51% of patients similarly sub- its ability to inhibit crystal aggregation and 336 280 mitted an inadequate sample based on the same agglomeration, properties that are not reflected by 337 281 definition.22 Often the clinician is faced with the un- reductions in supersaturation. Further complexity 338 282 comfortable situation of confronting the patient is demonstrated by the controversy about whether 339 283 regarding the adequacy issue, which usually leads to citrate prevents calcium phosphate stones.26 Anec- 340 284 repeat testing. Patients often acknowledge drinking dotal evidence suggests that citrate inhibits calcium 341 285 more fluids and adhering more tightly to prescribed phosphate stone recurrence, while the associated 342

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343 bicarbonaturia and increased urine pH tend to in- decreased recurrence rates. Among 108 patients 400 344 crease calcium phosphate supersaturation. Calcu- with single and mostly recurrent calcium based 401 345 lating supersaturation by alternative equations stones during 5 years, without pharmacological 402 346 such as JESS (Joint Expert Speciation System) may intervention 58% had no evidence of stone growth or 403 347 lead to different interpretations of these effects.27 new stone formation.8 Of all patients, 71% of those 404 348 An additional issue is that urine collections can with hypercalciuria and 47% with hyperuricosuria 405 349 be expensive, especially when accounting for repeat did not form new stones. 406 350 testing. Out-of-pocket costs for Litholink (Chicago, 407 351 Illinois) are more than $400 per test at the full rate 408 352 and less than $200 if discounted. Not all metabolic DISCUSSION AND FUTURE DIRECTIONS 409 353 stone conditions require frequent monitoring. For For a substantial population of stone formers, the 410 354 example, the management of idiopathic uric acid 24-hour urine collection offers hope in revealing the 411 355 nephrolithiasis does not necessitate 24-hour urine specific etiology of the disease. The alternative of 412 356 collections for pH monitoring. Spot urine pH testing remaining ignorant of urinary chemistry is admit- 413 357 is sufficient, inexpensive and easy. tedly unsatisfactory to patients and their physi- 414 358 We also noted that testing is not available in many cians. The test provides screening for certain 415 359 less developed countries. Even in the United States, metabolic conditions, such as primary hyper- 416 360 some municipal health care settings do not cover oxaluria and cystinuria. While it serves as the 417 361 testing and with the large number of Americans mainstay of the complete metabolic evaluation, 418 362 lacking health care coverage, many individuals do not there are has limitations to test interpretability. To 419 363 have access to testing. Therefore, it is incumbent on our knowledge data from the test have not reliably 420 364 the kidney stone community to consider how to pre- been used to predict recurrence or prognosticate 421 365 vent stone recurrence when testing is not possible. risk in the context of different dietary and phar- 422 366 macological management strategies. 423 367 Is Collection Needed for All High Risk Stone Sometimes no urinary abnormalities are found. 424 368 Formers? The AUA guidelines committee has recognized the 425 369 Not all stone formers need a complete metabolic dilemma of the “normal” 24-hour urine collection in 426 370 evaluation, as the risk of recurrence is different for the recurrent calcium stone former with no metabolic 427 371 each individual. Among idiopathic calcium based abnormalities.2 In guideline 17, which is listed as a 428 372 stone formers, more than 50% will have only 1 Standard, it states that in these individuals, thia- 429 373 recurrence in a lifetime and 10% will have more zides and/or potassium citrate should be considered 430 374 than 3 recurrences.28 Placebo arms of the different for those with “normal” test results.2 Perhaps one 431 375 intervention trials evaluating thiazides, allopurinol, may question what value the test adds in such cases. 432 376 citrate, phosphate and magnesium supplementation The stone clinic effect may reduce the real benefit 433 377 for recurrent calcium based stone formers have of the 24-hour urine collection. For a large subset of 434 378 shown a 0% to 61% decrease in the stone recurrence recurrent stone formers, perhaps it is warranted to 435 379 rate (the rate of stone events after vs before inter- trial a period of nonselective dietary changes rather 436 380 vention) and a remission rate (the absence of stone than repeat tests. Indeed, it is well established that 437 381 events and/or stone growth during the trial) of 20% high fluid intake29 and a low salt diet30 significantly 438 382½T1 to 86% (see table). The stone clinic effect refers to decrease stone recurrence without the addition of 439 383 regular clinic visits at which fluid and dietary re- pharmacological treatment.4 Fluid intake is low 440 384 minders alone are associated with significantly cost, accessible and safe with minimal side effects. 441 385 442 386 Stone clinic effect shown by stone recurrence and remission rates in placebo arms in recurrent stone formers 443 387 444 Stone Rate 388 No. Mean Followup % Formation % 445 389 References Participants (yrs) Control Regimen Pretreatment On Study Change Remission 446 390 Coe FL: Ann Intern Med 1977; 87: 404 34 3.2 Fluids þ diet 0.31 0.27 13 68 447 391 Ettinger B et al: Am J Med 1979; 67: 245 20, 26 2.9, 2.9 Placebo þ diet, diet 0.78, 0.57 0.33, 0.32 58, 44 70, 47 448 392 Johansson G et al: J Urol 1980; 124: 770 34 2.0 None 0.50 0.22 56 56 449 Brocks P et al: Lancet 1981; 2: 124 29 3.0 Placebo 0.70 0.11 84 83 393 Scholz D et al: J Urol 1982; 128: 903 26 1.0 Placebo Not applicable 0.23 Not applicable 77 450 394 Laerum and Larsen12 25 3.2 Placebo, diet þ fluids 0.56 0.33 41 52 451 395 Ettinger B et al: N Engl J Med 1986; 315: 1386 31 2.0 Placebo þfluids 0.71 0.26 63 42 452 Ettinger et al13 31 2.1 Placebo, diet þ fluids 0.57 0.22 61 55 396 Ohkawa M et al: Br J Urol 1992; 69: 571 93 2.1 Diet þ fluids Not applicable 0.31 Not applicable 86 453 397 Barcelo P et al: J Urol 1993; 150: 1761 20 3.0 Placebo 1.10 1.10 0 20 454 398 Hofbauer et al11 22 3.0 Diet þ fluids 1.80 0.70 61 27 455 10 þ 399 Ettinger et al 33 3.0 Placebo diet 0.57 0.27 52 36 456

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457 It is appreciated that stone formation and growth CONCLUSIONS 514 458 are more than physical chemistry phenomena in the The metabolic evaluation of stone formers with 24- 515 459 urinary milieu. The importance of trace elements, hour urine collections is recommended by current 516 460 including heavy metals, must be further defined guidelines and is increasingly viewed as a quality 517 461 and potentially incorporated into the metabolic metric in kidney stone care. However, the evidence 518 462 evaluation. The role of urinary proteins and their demonstrating that treatment based on the test is 519 463 involvement in promoting or inhibiting matrix for- superior to empirical or nonselected therapy is 520 464 mation needs additional study. Tissue level factors limited. The 24-hour urine collection is imperfect in 521 465 also must be accounted for, as the role of Randall predicting stone recurrence, stone composition or 522 466 plaques in idiopathic calcium based stones is well responses to treatment. Interpretation of the study 523 467 accepted. Finally, the interpretation of the multi- is complex and often subjective. Determining which 524 468 tude of urinary values may fall under the umbrella stone forming populations benefit most from the test 525 469 of complex data necessitating computer modeling, and developing additional tools to determine recur- 526 470 extrapolation and simulation. rence risk are needed. 527 471 We also acknowledge that spot urine collections 528 472 are not superior in providing clinically meaningful 529 473 metabolic diagnoses or judging responses to ther- APPENDIX 530 474 apy, except for monitoring urine pH in the Pros and Cons of 24-Hour Urine Collection 531 475 management of uric acid stones. It should also be Pros Cons 532 476 clear that the consequential diagnosis of primary Guideline supported Complexity in interpretation 533 477 hyperoxaluria is unlikely to be made without a Objective, quantifiable data Limited ability to predict recurrence 534 478 24-hour urine collection. Finally, the extent of Can check compliance with fluids Limited ability to predict response 535 and medications 479 dietary sodium ingestion, which is often occult and Some view as convenient Some view as inconvenient 536 480 related to eating processed foods, is best assessed Limits diet or medication prescription May require repeat testing 537 481 and communicated to patients by the 24-hour to specific issues 538 Gives hope to lifelong disease Cost 482 collection. 539 483 540 484 541 485 542 486 REFERENCES 543 487 1. Ljunghall S, Lithell H and Skarfors E: Prevalence idiopathic calcium urolithiasis. J Urol 1983; 15. Trinchieri A, Ostini F, Nespoli R et al: A pro- 544 488 of renal stones in 60-year-old men. A 10-year 130: 1115. spective study of recurrence rate and risk factors 545 489 follow-up study of a health survey. Br J Urol for recurrence after a first renal stone. J Urol 546 1987; 60: 10. 9. Fink HA, Wilt TJ, Eidman KE et al: Medical 1999; 162: 27. 490 management to prevent recurrent nephrolithiasis 547 491 2. Pearle MS, Goldfarb DS, Assimos DG et al: in adults: a systematic review for an American 16. Pak CY: Should patients with single renal stone 548 492 Medical management of kidney stones: AUA College of Physicians Clinical Guideline. Ann occurrence undergo diagnostic evaluation? J 549 guideline. J Urol 2014; 192: 316. 127: 493 Intern Med 2013; 158: 535. Urol 1982; 855. 550 3. Skolarikos A, Straub M, Knoll T et al: Metabolic 494 10. Ettinger B, Pak CY, Citron JT et al: Potassium- 17. Gentle DL, Stoller ML, Bruce JE et al: Geriatric 551 evaluation and recurrence prevention for urinary 158: 495 magnesium citrate is an effective prophylaxis urolithiasis. J Urol 1997; 2221. 552 stone patients: EAU guidelines. Eur Urol 2015; 496 against recurrent calcium oxalate nephrolithiasis. 553 67: 750. 18. Pak CY, Poindexter JR, Adams-Huet B et al: J Urol 1997; 158: 2069. 497 Predictive value of kidney stone composition in 554 4. Fink HA, Wilt TJ, Eidman KE et al: Recurrent 498 the detection of metabolic abnormalities. Am J 555 Nephrolithiasis in Adults: Comparative Effec- 11. Hofbauer J, Hobarth K, Szabo N et al: Alkali Med 2003; 115: 26. 499 tiveness of Preventive Medical Strategies. citrate prophylaxis in idiopathic recurrent calcium 556 d 500 Rockville: Agency for Healthcare Research and oxalate urolithiasis a prospective randomized 19. Curhan GC, Willett WC, Speizer FE et al: Twenty- 557 73: 501 Quality 2012. study. Br J Urol 1994; 362. four-hour urine chemistries and the risk of kidney 558 502 stones among women and men. Kidney Int 2001; 559 5. Milose JC, Kaufman SR, Hollenbeck BK et al: 12. Laerum E and Larsen S: Thiazide prophylaxis 59: 2290. 503 Prevalence of 24-hour urine collection in high of urolithiasis. A double-blind study in 560 191: 504 risk stone formers. J Urol 2014; 376. general practice. Acta Med Scand 1984; 20. Taylor EN and Curhan GC: Differences in 24-hour 561 505 215: 383. 562 6. Dauw CA, Alruwaily AF, Bierlein MJ et al: Pro- urine composition between black and white 506 women. J Am Soc Nephrol 2007; 18: 654. 563 vider variation in the quality of metabolic stone 13. Ettinger B, Citron JT, Livermore B et al: Chlor- 507 management. J Urol 2015; 193: 885. 564 thalidone reduces calcium oxalate calculous 21. Sawyer MD, Dietrich MS, Pickens RB et al: 508 7. Kocvara R, Plasgura P, Petrik A et al: A recurrence but magnesium hydroxide does not. J Adequate or not? A comparison of 24-hour 565 139: 509 prospective study of nonmedical prophylaxis Urol 1988; 679. urine studies for renal stone prevention 566 510 after a first kidney stone. BJU Int 1999; by creatinine to weight ratio. J Endourol 2013; 567 84: 393. 14. Borghi L, Schianchi T, Meschi T et al: Comparison 27: 366. 511 of two diets for the prevention of recurrent 568 512 8. Hosking DH, Erickson SB, Van den Berg CJ stones in idiopathic hypercalciuria. N Engl J Med 22. McGuire BB, Bhanji Y, Sharma V et al: Predicting 569 513 et al: The stone clinic effect in patients with 2002; 346: 77. patients with inadequate 24- or 48-hour urine 570

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571 collections at time of metabolic stone evalua- 25. Moreira DM, Friedlander JI, Hartman C et al: 28. Strohmaier WL: Course of calcium stone disease 633 572 tion. J Endourol 2015; 29: 730. Using 24-hour urinalysis to predict stone type. J without treatment. What can we expect? Eur 634 573 Urol 2013; 190: 2106. Urol 2000; 37: 339. 635 574 23. Whitson JM, Cooperberg MR, Stackhouse GB 636 et al: Urinary citrate levels do not correlate with 26. Goldfarb DS: A woman with recurrent calcium 29. Borghi L, Meschi T, Amato F et al: Urinary vol- 575 637 urinary pH in patients with urinary stone for- phosphate kidney stones. Clin J Am Soc Nephrol ume, water and recurrences in idiopathic calcium 576 mation. Urology 2007; 70: 634. 2012; 7: 1172. nephrolithiasis: a 5-year randomized prospective 638 577 study. J Urol 1996; 155: 839. 639 578 24. Parks JH, Coward M and Coe FL: Correspon- 27. Rodgers AL, Allie-Hamdulay S, Jackson G et al: 640 579 dence between stone composition and urine Simulating calcium salt precipitation in the 30. Taylor EN, Fung TT and Curhan GC: DASH-style 641 580 supersaturation in nephrolithiasis. Kidney Int nephron using chemical speciation. Urol Res diet associates with reduced risk for kidney 642 581 1997; 51: 894. 2011; 39: 245. stones. J Am Soc Nephrol 2009; 20: 2253. 643 582 644 583 645 584 646 585 647 586 EDITORIAL COMMENT 648 587 649 588 The value of 24-hour urine collection is put under decreases recurrence (reference 19 in article).2 650 589 suspicion for urolithiasis diagnosis and recurrence. Empirical treatment benefits with citrate potas- 651 590 Parks et al noted that only a single 24-hour urine sium and/or thiazides are possible but followup 652 591 653 collection is not enough.1 This analysis has limita- studies to eventually make the diagnosis have not 592 654 593 tions, including more than 1 biochemical abnor- been previously reported. Diet and increasing fluids 655 594 mality present, borderline values and weekend are of great value but not always sufficient, espe- 656 595 collection which could vary the diet. However, 2 cially in hypercalciuric patients who require thia- 657 596 consecutive collections decrease variability and zides and increasing doses to achieve metabolic 658 597 make results trustworthy. Weekend diet differences control according to followups. 659 598 are the same for stone formers compared to non- 660 599 formers with a genetic component in the latter 661 Rodolfo Spivacow 600 (forming stones is not a wish but a capacity). 662 601 Medical Department 663 Defining recurrence is difficult but countless papers Instituto de Investigaciones Metabolicas 602 664 show that correcting biochemical abnormalities Buenos Aires, Argentina 603 665 604 666 605 667 606 REFERENCES 668 607 669 167: 608 1. Parks JH, Goldfisher E and Asplin JR: A single 24-hour urine collection is inadequate for the medical evaluation of nephrolithiasis. J Urol 2002; 1607. 670 609 2. Robinson MR, Leitao VA, Haleblian GE et al: Impact of long-term potassium citrate therapy on urinary profiles and recurrent stone formation. J Urol 2009; 181: 1145. 671 610 672 611 673 612 674 613 675 614 676 615 REPLY BY AUTHORS 677 616 678 617 The perspective of the commentator is what pre- testing may be as good as specific therapy guided by 679 618 cisely motivated our effort to challenge how we a 24-hour urine collection for the majority of idio- 680 619 prescribe and interpret the 24-hour urine collection. pathic calcium stone formers. 681 620 Our intention was not to focus on whether per- The prognostic capacity of 24-hour urine collection 682 621 683 forming 1 or 2 collections is better or which day of values individually and in combination, along with 622 684 623 the week is optimal to perform this test. Rather, as a supersaturation indexes, has not been rigorously 685 624 starting point, our intention was to generate a dis- studied. Until we perform the necessary prospective 686 625 cussion on how we can better define and refine who studies, we will not know the answers to these ques- 687 626 should receive testing. tions. Indeed, the 24-hour urine collection provides 688 627 The stone clinic effect is known to be associated value for the care of many of our patients with kidney 689 628 with a decrease in stone recurrence in the absence stone. We should not let our reliance on this test lead 690 629 of 24-hour urine testing. Empirical drug therapy to stagnation of the development of additional tools to 691 630 with potassium citrate and/or thiazides without help prevent kidney stone recurrence. 692 631 693 632 694

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