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1 This is the written version of our Hot Topic video presentation available at: MayoMedicalLaboratories.com/hot-topics Welcome to Mayo Medical Laboratories Hot Topics. These presentations provide short discussion of current topics and may be helpful to you in your practice. 1
2 Our speaker for this program is Dr. John Lieske, Professor of Medicine at Mayo Clinic, Medical Director of the Renal Testing Laboratory in the Department of Laboratory Medicine and Pathology, and a Consultant in the Division of Nephrology and Hypertension at Mayo Clinic in Rochester, Minnesota. Dr. Lieske provides a 2-part update on kidney stones. Part 2 discusses the risks for recurrent stones and the search for rare causes of kidney stones. Thank you, Cara 2
3 I have the following disclosures; our work described here has funding from National Institute of Diabetes and Digestive and Kidney Diseases, the Rare Diseases Clinical Research Network and then also the National Center for Advancing Translational Sciences. In part 2 of our series of nephrolithiasis we will focus on the factors that predict risk of stone recurrence and clues to search for a rare cause of kidney stone disease. 3
4 When seeing a person with a first-time kidney stone, the question often arises: how likely are they to form a second stone? This might influence our inclination to treat with medications for stone prevention. This case can help to illustrate our point: A 30-year old, white female presents with renal colic and gross hematuria from a 10- mm left renal pelvic stone. The stone is uteroscopically removed and is 100% calcium oxalate. A nonobsructing upper-pole 8-mm stone was also removed. There was family history of stones, but this is her first stone event. She had similar symptoms 5 years ago, but they resolved on their own and no stone was ever seen. Questions that arise are: What is her risk of future symptomatic stones? How aggressively should she be treated with diet and medications to prevent recurrence? Would she be a good candidate for a 5-year clinical trial to prevent stone events? 4
5 Olmsted County provides an ideal opportunity to ask these sorts of questions. The population is representative of much of the United States, and most persons are seen at local health facilities including Mayo Clinic. The Rochester Epidemiology Project was set up to facilitate these sorts of studies. 5
6 Shown here, the overall risk of stone recurrence in Olmsted County after a first kidney stone is about 32% after 10 years. 6
7 We have recently carefully examined this risk looking at all first-time kidney stone formers in Olmsted County between 1984 and
8 Many demographic factors were important. As shown here, the younger stone patients were most likely to recur. 8
9 Males were also more likely to recur. 9
10 Those with a family history were most likely to recur. 10
11 Those with a uric acid stones were especially likely to recur. 11
12 Thus, we used these clinical features to construct a multivariable analysis that could be used to predict the risk that a first-time stone former would recur. 12
13 This slide contains the factors that were significant in a multivariable model. Using our patient as an example, we can rate her for each. Overall she earns 329 points. 13
14 This slide contains the factors that were significant in a multivariable model. Using our patient as an example, we can rate her for each. Overall she earns 329 points. 14
15 Risk of recurrence at 2, 5, and 10 years is predicted to be 30%, 50%, and 70%, respectively. This graph also illustrates how variable these risks would be depending on the score. These numbers might influence our enthusiasm for various treatment regimens. 15
16 This nomogram is now available as an app through Qx calculator. 16
17 Not all stones are created equal. Some have genetic causes that are associated with very high risk of recurrence, and even renal damage, chronic kidney disease, and renal failure. Thus, it s important not to miss these diseases. 17
18 The Rare Kidney Stone Consortium, shown here, is funded by the NIH and studies these diseases. 18
19 The common pathogenic pathway for these diseases seems to be crystal deposition in the kidney, followed by scarring, fibrosis, and renal failure. 19
20 Given the importance of their early diagnosis, we will briefly review clues that a stone patient may have one if these rare causes. History and physical examination clues include: Having first stone as a preadolescent Having acute kidney injury Having a reddish-brown diaper stain, which is seen with APRT deficiency Having growth retardation, or Having a family history of stones or nephrocalcinosis or unexplained kidney failure 20
21 On medical imaging, typically noncontrast CT scanning, clues include: The presence of nephrocalcinosis The presence of radiolucent kidney stones that are known not to be uric acid and a high stone burden. 21
22 Clues on the urinalysis include: Certain crystals that are characteristic of a specific disease. These include: Dihydroxyadenine crystals, which are seen in APRT deficiency Cystine crystals are typical hexagons Calcium oxalate mono or dehydrate crystals, which can be seen in primary hyperoxaluria (PH) If unidentified crystals are seen, they might be dihydroxyadenine. This could point to APRT deficiency, and Mild-moderate proteinuria is a clue to Dent disease; in this case the urine protein will contain low-molecular weight forms. One can check a urine retinol binding protein or alpha 1 microglobulin to detect this more specifically. 22
23 Shown on this slide are typical calcium oxalate dihydrate, cysteine, and DHA crystals. The characteristic brown DHA crystals are shown under phase contrast, as well as under polarized light with the cross pattern apparent. Amorphous calcium phosphate crystals might be seen in Dent disease, but this is a common finding in the urinalysis and not specific. 23
24 A stone analysis can be very helpful. A DHA stone makes the diagnosis of APRT deficiency; a cystine stone makes the diagnosis of cystinuria. Patients with PH should have calcium oxalate stones, although this is not a specific finding. Patients with Dent disease can have calcium phosphate or calcium oxalate stones. 24
25 The presence of both kidney stones and reduced kidney function in the same patient should raise suspicion of one of these rare diseases, especially in children. 25
26 Certain features on a 24-hour urine study raise the likelihood of one of these diseases. (1) A markedly increased urinary oxalate excretion suggests primary hyperoxaluria. A cutoff to suspect ph is greater than 2 times normal without intestinal malabsorption. (2) A positive urinary sodium nitropusside test suggests cystinuria. This should be confirmed with a quantitative urinary cystine. (3) The combination of radiolucent stones and alkaline urine ph suggests APRT deficiency. Specifically this patient does not have a uric acid stone, which is also radiolucent, but occurs only in acidic urine. And, (4) Hypercalciuria plus proteinuria in younger male suggests Dent disease 26
27 In summary clues to a rare stone include: Presentation at a young age Frequent stones with or without nephrocalcinosis A strong family history of stones especially if kidney failure is present Chronic kidney disease Unusual stone type therefore, all stones should be analyzed. This point cannot be overemphasized. Unusual urine crystals Unexplained proteinuria (especially in younger males) And, for details regarding algorithms to make the diagnosis of these rare diseases, see the reference noted (Edvardsson VE, et al: Pediatric Nephrology 2013 for published algorithms). 27
28 This slide summarizes our take home points from the 2 series on nephrolyisis. Different stones are more likely in different people: Not all kidney stones are created equal Treatments differ by stone type and cause Thus, all stones should be analyzed and 24-hour urine studies are required to guide treatment Clinical characteristics can predict the risk of occurrence Missing certain causes of stones can have severe consequences 28
29 Thank you. 29
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