The interest of oral calcium loads test in the diagnosis and management of pediatric nephrolithiasis with hypercalciuria: Experience from a tertiary pediatric centre

Mosca, Mélodie; Bertholet‐Thomas, Aurélia; Lemoine, Sandrine; Garnier, C.; Machon, Christelle; Molin, Arnaud; Dubourg, Laurence; Bacchetta, Justine

doi:10.1016/j.jpurol.2020.05.160

Cited by 5 publications

(3 citation statements)

References 56 publications

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“…The second step is to identify favoring factors, notably urological abnormalities, chronic digestive diseases inducing malabsorption, drug intake, and/or history of infections. Table 1 summarizes the biological evaluation that should be performed when evaluating a child with a first episode of lithiasis [ 4 , 28 ]. In Table 2 there are pediatric references about plasmatic and urinary electrolytes [ 29 ]…”

Section: Specificities Of Urolithiasis In Pediatricsmentioning

confidence: 99%

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Hydration and Nephrolithiasis in Pediatric Populations: Specificities and Current Recommendations

et al. 2023

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Renal lithiasis is less frequent in children than in adults; in pediatrics, lithiasis may be caused by genetic abnormalities, infections, and complex uropathies, but the association of urological and metabolic abnormalities is not uncommon. The aim of this study is to provide a synthesis of nephrolithiasis in children and to emphasize the role of hydration in its treatment. As an etiology is reported in 50% of cases, with a genetic origin in 10 to 20%, it is proposed to systematically perform a complete metabolic assessment after the first stone in a child. Recent data in the field reported increased incidence of pediatric urolithiasis notably for calcium oxalate stones. These changes in the epidemiology of stone components may be attributable to metabolic and environmental factors, where hydration seems to play a crucial role. In case of pediatric urolithiasis, whatever its cause, it is of utmost importance to increase water intake around 2 to 3 L/m2 per day on average. The objective is to obtain a urine density less than 1010 on a dipstick or below 300 mOsm/L, especially with the first morning urine. Some genetic diseases may even require a more active 24 h over-hydration, e.g., primary hyperoxaluria and cystinuria; in such cases naso-gastric tubes or G-tubes may be proposed. Tap water is adapted for children with urolithiasis, with limited ecological impact and low economical cost. For children with low calcium intake, the use of calcium-rich mineral waters may be discussed in some peculiar cases, even in case of urolithiasis. In contrast, sugar-sweetened beverages are not recommended. In conclusion, even if parents and patients sometimes have the feeling that physicians do not propose “fancy” therapeutic drugs, hydration and nutrition remain cornerstones of the management of pediatric urolithiasis.

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Section: Specificities Of Urolithiasis In Pediatricsmentioning

confidence: 99%

“…Novel therapies based on RNA interference have recently emerged, and these therapies are a real game changer for managing patients with PH1, likely improving their quality of life and potentially preventing the need for transplantation [ 28 , 38 , 54 ].…”

Section: Place Of Hydration In Nephrolithiasis Treatmentmentioning

confidence: 99%

Hydration and Nephrolithiasis in Pediatric Populations: Specificities and Current Recommendations

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“…The examinations realized during the visits will be performed speci cally for the study: urine, and blood analysis, electrocardiogram, Dual X-ray absorptiometry (DXA), renal ultrasounds, dietetic questionnaires, oral calcium load tests (12). Bone evaluation with DXA : femoral neck (FN), lumbar spine vertebra 2 to 4 (LS2-4) and total body (TB) areal bone mineral density (aBMD, g.cm-2).…”

Section: Patients Will Receive Uconazole or Placebo During 18 Weeksmentioning

confidence: 99%

Fluconazole in Hypercalciuric Patients with Increased 1,25(OH)2D Levels: The Prospective, Randomized, Placebo-Controlled, Double Blind FLUCOLITH Trial.

Bertholet‐Thomas

Portefaix

Flammier

et al. 2022

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BackgroundHypercalciuria is one of the most frequent metabolic disorders associated with nephrolithiasis and/or nephrocalcinosis possibly leading to chronic kidney disease (CKD) and bone complications in adults. Orphan diseases with different underlying primary pathophysiology share inappropriately increased 1,25(OH)2D levels and hypercalciuria, e.g., hypersensitivity to vitamin D and renal phosphate wasting. Their management is challenging, typically based on hyperhydration and dietary advice. The antifungal azoles are known to inhibit the 1α-hydroxylase and therefore decrease 1,25(OH)2D levels; they are commonly used, with well described pharmacokinetic and tolerability data. Fluconazole has been successfully reported to reduce calciuria in patients with CYP24A1 or SLC34A3 mutations, with no safety warnings. Thus, based on these case reports, we hypothesize that fluconazole is effective to decrease and normalize calciuria in patients with hypercalciuria and increased 1,25(OH)2D levels.MethodsThe FLUCOLITH trial is a prospective, interventional, randomized in parallel groups (1:1), placebo-controlled, double blind trial. A total of 60 patients (10-60years) with nephrolithiasis and/or nephrocalcinosis history, hypercalciuria (> 0.1 mmol/kg/d), increased 1,25(OH)2D levels (> 150 pmol/L) and 25-OH-D levels >20 nmol/L, will be included. Inclusions will be performed only from mid-September to the beginning of February to avoid bias due to sunlight-induced vitamin D synthesis. The primary endpoint will be the proportion of patients with normalization of 24-hour calciuria between baseline and 16 weeks, or with a relative decrease of at least 30% of 24-hour calciuria in patients who still display at W16 a 24-hour hypercalciuria. DiscussionThe current challenge is to propose an efficient treatment to patients with hypercalciuria and increased 1,25(OH)2D levels in order to prevent later complications and notably CKD that can ultimately lead to end-stage renal disease. Based on improvement of knowledge in phosphate/calcium metabolism, pathophysiology and genetics, the “off-label” use of fluconazole was recently reported to be useful in hypercalciuric patients with increased 1,25(OH)2D levels. Thus, the FLUCOLITH study is a unique opportunity to develop a new indication of a well-known and not expensive drug in orphan renal diseases, the ultimate objective being the secondary prevention of CKD worsening in these patients. Trial RegistrationClinicalTrial.gov, ID: identifier: NCT04495608. Registered on July 23rd, 2020

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Pediatric urolithiasis: what can pediatricians expect from radiologists?

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The interest of oral calcium loads test in the diagnosis and management of pediatric nephrolithiasis with hypercalciuria: Experience from a tertiary pediatric centre

Cited by 5 publications

References 56 publications

Hydration and Nephrolithiasis in Pediatric Populations: Specificities and Current Recommendations

Hydration and Nephrolithiasis in Pediatric Populations: Specificities and Current Recommendations

Fluconazole in Hypercalciuric Patients with Increased 1,25(OH)2D Levels: The Prospective, Randomized, Placebo-Controlled, Double Blind FLUCOLITH Trial.

Pediatric urolithiasis: what can pediatricians expect from radiologists?

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