Introduction
Methods
Analytical procedure
Questions and consensus statements
Questions #1 and #2
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Studies to evaluate the risk of CKD according to etiology and composition of renal stones.
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Registry studies on the effect of different urological treatments of renal stones. This requires a minimum standard for data acquisition (e.g. stone burden, stone composition, concomitant obstruction, concomitant infection, urological procedure(s), repeated procedures.
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Methods for the evaluation of the renal damage in stone formers.
Questions #3 and #4
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Studies to evaluate which stone formers are at most risk of bone disease.
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Studies to evaluate which treatment(s) for recurrent stones most favorably increase bone mass.
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Studies to evaluate which treatment(s) for osteoporosis in stone formers most favorably increase bone mass.
Question #5
1. Hyperparathyroidism |
2. Hyperthyroidism |
3. Sarcoidosis |
4. Vitamin D excess |
5. Calcium supplements |
6. Prolonged immobilization |
7. Clinical evidence of bone disease |
8. Malignant neoplasms |
9. dRTA |
10. MSK |
11. Primary hyperoxaluria |
12. Enteric hyperoxaluria |
13. Bowel disease |
14. Chronic pancreatitis |
15. Vitamin C supplements |
16. Chronic diarrhea |
17. Lithogenic drugs |
18. Urinary infection |
19. Gouty diathesis |
20. Cystinuria |
Conditions |
Hypercalciuria
|
Hypocitraturia
|
Hyperoxaluria
|
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Primary hyperparathyroidism | ∙ | ||
Prolonged immobilization | ∙ | ∙ | |
Incomplete dRTA | ∙ | ∙ | |
Drugs and vitamin excess | ∙ (vit. D) | ∙ (orlistat, vit. C) | |
Chronic diarrhea | ∙ | ||
Chronic pancreatitis, Crohn’s disease, gastric bypass procedures, or small bowel resections | ∙ | ∙ | |
Nephrocalcinosis | ∙ | ∙ | ∙ |
Genetic conditions associated with stones (including primary hyperoxaluria) | ∙ | ∙ | ∙ |
MSK | ∙ | ∙ |
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Studies on the pathogenesis of hypercalciuria
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Studies on the pathogenesis of brushite stones
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Studies on the relationship between ESWL and brushite stones
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Studies on circadian variation in urine composition
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Discovery of urinary markers of idiopathic calcium nephrolithiasis and metabolic activity
Questions #6 and #7
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Clinical and basic studies in the area of incomplete distal RTA and in CN associated with incomplete distal RTA.
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Studies in which 24-h or fasting urinary pH should be used as a guide to indicate which stone formers should be tested for incomplete distal RTA.
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Studies on easier test protocols for diagnosing incomplete distal RTA.
Question #8
Overproduction | Renal leak |
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Gout/metabolic syndrome | Uricosuric agents |
Dietary purine overload | Rare transporter diseases |
Catabolic states | |
Rare monogenic diseases of purine metabolism |
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Studies on the exact physicochemical basis and on the relative contributions of each model.
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Development of the in silico way (akin to EQUIL or JESS) of quantitatively predicting the risk of calcium stones conferred by urine uric acid/urate.
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Studies on dose–effect of uricosuria on calcium stone risk.
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Studies on the degree of lowering uricosuria that should be targeted.
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Studies on the interaction of hyperuricosuria with other urinary stone risks.
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Studies on whether the threshold to treat and the therapeutic target differ depending on the presence and degree of hypercalciuria, hypocitraturia, and hyperoxaluria.
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Studies on the mechanism of the allopurinol stone-preventive effect.
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Therapeutic trial on HUCU as here defined.
Question #9
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Studies on the performance of different diagnostic algorithms in identifying secondary forms of nephrolithiasis.
Question #10
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Studies on standardization of methods for ULM determination and application to larger numbers of stone forming and non-stone forming subjects.
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Studies investigating whether follow-up and treatment guided by urine RS determination decreases stone recurrences.
Question #11
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Crystal aggregation (agglomeration) and crystal-cell interaction may be of clinical use in the future. At present, data are too scarce. For a better understanding of the mechanism of stone formation, it may be worthwhile to combine urine crystal analysis with endoscopic analysis of papilla, correlating it with the presence of plaques and plugs.
Question #12
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Studies on the role of crystallization inhibitors and crystal aggregation inhibitors in stone formation in the interstitium (Randall’s plaque precursors), and in the interface with papillary deposits (Randall’s plaque), and ductal plugs.
Question #13
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Development of papillary scoring systems, including validation by external observers, with subsequent study of the utility of each scoring system in clinical practice.
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Studies of the correlation of papillary pathology with prognosis of disease and prediction of recurrence of stones.
Question #14
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Educational work needs to be done to improve existing practices of stone analysis.
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Nomenclature for stone components needs to be standardized.
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More work is needed on stone morphology to implement it in stone analysis.
Questions #15, #16 and #17
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Studies on markers that predict stone recurrence.
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Studies on metabolic markers that distinguish metabolically active vs. metabolically inactive stone formers.
Questions #18 and #19
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Studies on the fate of asymptomatic stone formers. Should patients with renal stone(s) incidentally found in imaging studies undergo a metabolic evaluation and/or follow-up?
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New stone formation and stone growth are not always distinguishable depending on different imaging modalities. Future observational studies or RCTs should employ sensitive and, more importantly, standardized detection methods. They should define an absolute stone size or growth rate threshold(s) in order to ascertain the presence of baseline residual stones, and then to establish measurement of stone growth. The use of standard modalities and appropriate testing frequencies, to ascertain incident radiographic stones should be defined. Patients with asymptomatic stone growth, radiographic stone recurrence and/or asymptomatic stone passage should be followed untreated for several years for symptomatic stone recurrence to help determine whether and under what circumstances these measures can serve as appropriate surrogates for symptomatic stone recurrence. RCTs should separately report the outcomes of symptomatic and radiographic stones, describe the laboratory and radiographic testing that participants undergo, including their cumulative radiation exposure.
Question #20
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Controlled trials of the effects of different types of beverages, including bicarbonate-rich mineral water and water with different calcium content, on the rate of stone recurrence in patients with CN are warranted.
Question #21
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RCTs on the value of complex dietary patterns, such as the Mediterranean diet, in primary and secondary prevention of nephrolithiasis are warranted.
Questions #22, #23 and #24
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RCTs on the pharmacological prevention with thiazides of recurrent calcium stone disease with different biochemical phenotypes (normo- and hypercalciuric, etc.).
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Since the pharmacological armamentarium for renal stone prevention is quite limited there is need of studies investigating new drugs to prevent stone recurrence.
Question #25
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Due to the potential risk of calcium phosphate stone formation with alkali treatment, alternatives to alkali treatment should be tested in prospective clinical studies using citric acid vs. potassium citrate or thiazide + potassium chloride vs. thiazide + potassium citrate in this population.
Questions #26 and #27
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As part of an integrated clinical management pathway for nephrolithiasis patients, the nephrologist and urologist—ideally in collaboration—will have to face the development of shared protocols for the evaluation of stone formers and for defining cooperation.
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The evaluation of Quality and cost/benefit ratio of the protocols for renal stone forming patients.
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Cost/benefit analysis of instrumental investigations for the follow-up of renal stone forming patients (economic cost, radiological risks).