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Pediatric Nephrolithiasis. Healthcare (Basel) 2023; 11:healthcare11040552. [PMID: 36833086 PMCID: PMC9957182 DOI: 10.3390/healthcare11040552] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 01/30/2023] [Accepted: 02/10/2023] [Indexed: 02/15/2023] Open
Abstract
The prevalence of pediatric nephrolithiasis has increased dramatically in the past two decades for reasons that have yet to be fully elucidated. Workup of pediatric kidney stones should include metabolic assessment to identify and address any risk factors predisposing patients to recurrent stone formation, and treatment should aim to facilitate stone clearance while minimizing complications, radiation and anesthetic exposure, and other risks. Treatment methods include observation and supportive therapy, medical expulsive therapy, and surgical intervention, with choice of treatment method determined by clinicians' assessments of stone size, location, anatomic factors, comorbidities, other risk factors, and preferences and goals of patients and their families. Much of the current research into nephrolithiasis is restricted to adult populations, and more data are needed to better understand many aspects of the epidemiology and treatment of pediatric kidney stones.
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Ferre N, Parada E, Balaguer A, Feliu A, Roqué-Figuls M, Franco JVA, Escribano J. Pharmacological interventions for preventing complications in patients with idiopathic hypercalciuria: A systematic review. Nefrologia 2022; 42:506-518. [PMID: 36792305 DOI: 10.1016/j.nefroe.2021.04.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 04/03/2021] [Indexed: 06/18/2023] Open
Abstract
OBJECTIVE To assess the effects of pharmacological interventions in patients with idiopathic hypercalciuria. METHODS We performed a search of multiple databases, trial registries, grey literature and conference proceedings up to October 2019. We included randomized and quasi-randomized controlled trials that examined any pharmacological intervention for preventing complications of idiopathic hypercalciuria (given for at least four months and six of follow-up). The primary outcomes were stone-free patients, urinary symptoms and severe adverse events. RESULTS We included five RCTs (n=446 patients, all adults, 4 in individuals with kidney stones and 1 in postmenopausal women with osteoporosis). Diuretics were likely to increase the number of stone-free patients (RR 1.61, 95% CI 1.33-1.96, moderate quality of evidence (QoE)); 274 more stone-free patients/1000 patients treated (95% CI: 148-432) and produced a slight decrease in the stone formation rate (mean difference -0.18, 95% CI -0.30 to -0.06, low QoE); 180 fewer stones/year/1000 patients treated (95% CI: 300 r to 60). No data on urinary symptoms were reported. The association between diuretic use and severe adverse events was uncertain (RR 5.00, 95% CI 0.60-41.88, very low QoE); 4 more severe adverse events/1000 patients treated (95% CI: 0 fewer to 39 more). CONCLUSIONS The addition of diuretics to a normal or modified diet probably reduces the number of stone recurrences and may decrease the stone formation rate. It is uncertain whether diuretics increase the occurrence of severe adverse events. There were no studies investigating other outcomes or in children.
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Affiliation(s)
- Natalia Ferre
- Universitat Rovira i Virgili, School of Medicine, Pediatric Research Unit, Sant Llorenç 21, 43201 Reus, Spain
| | - Ester Parada
- Universitat Rovira i Virgili, School of Medicine, Pediatric Research Unit, Sant Llorenç 21, 43201 Reus, Spain; Department of Pediatrics, Hospital Universitari de Tarragona Joan XXIII, Dr. Mallafré Guasch 4, 43005 Tarragona, Spain
| | - Albert Balaguer
- Department of Pediatrics, Hospital Universitari General de Catalunya, Pere i Pons 1, 08195 Sant Cugat del Vallés, Barcelona, Spain; Universitat Internacional de Catalunya, Carrer de la Immaculada 22, 08017 Barcelona, Spain
| | - Albert Feliu
- Universitat Rovira i Virgili, School of Medicine, Pediatric Research Unit, Sant Llorenç 21, 43201 Reus, Spain; Department of Pediatrics, Hospital Universitari St Joan de Reus, Avinguda del Doctor Josep Laporte 2, 43204 Reus, Spain
| | - Marta Roqué-Figuls
- Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau), CIBER Epidemiología y Salud Pública (CIBERESP), Sant Quintí 77-79, 08041 Barcelona, Spain
| | - Juan Victor A Franco
- Argentine Cochrane Centre, Instituto Universitario Hospital Italiano, Potosí 4265, C1199 CABA Buenos Aires, Argentina
| | - Joaquín Escribano
- Universitat Rovira i Virgili, School of Medicine, Pediatric Research Unit, Sant Llorenç 21, 43201 Reus, Spain; Department of Pediatrics, Hospital Universitari St Joan de Reus, Avinguda del Doctor Josep Laporte 2, 43204 Reus, Spain.
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Penido MGMG, Tavares MDS. Beyond kidney stones: Why pediatricians should worry about hypercalciuria. World J Clin Pediatr 2021; 10:137-150. [PMID: 34868890 PMCID: PMC8603641 DOI: 10.5409/wjcp.v10.i6.137] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 08/08/2021] [Accepted: 10/31/2021] [Indexed: 02/06/2023] Open
Abstract
The incidence of urolithiasis (UL) is increasing, and it has become more common in children and adolescents over the past few decades. Hypercalciuria is the leading metabolic risk factor of pediatric UL, and it has high morbidity, with or without lithiasis as hematuria and impairment of bone mass. The reduction in bone mineral density has already been described in pediatric idiopathic hypercalciuria (IH), and the precise mechanisms of bone loss or failure to achieve adequate bone mass gain remain unknown. A current understanding is that hypercalciuria throughout life can be considered a risk of change in bone structure and low bone mass throughout life. However, it is still not entirely known whether hypercalciuria throughout life can compromise the quality of the mass. The peak bone mass is achieved by late adolescence, peaking at the end of the second decade of life. This accumulation should occur without interference in order to achieve the peak of optimal bone mass. The bone mass acquired during childhood and adolescence is a major determinant of adult bone health, and its accumulation should occur without interference. This raises the critical question of whether adult osteoporosis and the risk of fractures are initiated during childhood. Pediatricians should be aware of this pediatric problem and investigate their patients. They should have the knowledge and ability to diagnose and initially manage patients with IH, with or without UL.
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Affiliation(s)
- Maria Goretti Moreira Guimarães Penido
- Pediatric Nephrology Unit, Nephrology Center, Santa Casa de Belo Horizonte Hospital, CEP 30150320, Belo Horizonte, Minas Gerais, Brazil
- Pediatric Nephrology Unit, Pediatric Department, Clinics Hospital, Universidade Federal de Minas Gerais, CEP 30130100, Belo Horizonte, Minas Gerais, Brazil
| | - Marcelo de Sousa Tavares
- Pediatric Nephrology Unit, Nephrology Center, Santa Casa de Belo Horizonte Hospital, CEP 30150320, Belo Horizonte, Minas Gerais, Brazil
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Ferre N, Parada E, Balaguer A, Feliu A, Roqué-Figuls M, Franco JVA, Escribano J. Pharmacological interventions for preventing complications in patients with idiopathic hypercalciuria: A systematic review. Nefrologia 2021; 42:S0211-6995(21)00150-8. [PMID: 34393000 DOI: 10.1016/j.nefro.2021.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Revised: 03/23/2021] [Accepted: 04/03/2021] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE To assess the effects of pharmacological interventions in patients with idiopathic hypercalciuria. METHODS We performed a search of multiple databases, trial registries, grey literature and conference proceedings up to October 2019. We included randomized and quasi-randomized controlled trials that examined any pharmacological intervention for preventing complications of idiopathic hypercalciuria (given for at least four months and six of follow-up). The primary outcomes were stone-free patients, urinary symptoms and severe adverse events. RESULTS We included five RCTs (n=446 patients, all adults, 4 in individuals with kidney stones and 1 in postmenopausal women with osteoporosis). Diuretics were likely to increase the number of stone-free patients (RR 1.61, 95% CI 1.33-1.96, moderate quality of evidence (QoE)); 274 more stone-free patients/1000 patients treated (95% CI: 148-432) and produced a slight decrease in the stone formation rate (mean difference -0.18, 95% CI -0.30 to -0.06, low QoE); 180 fewer stones/year/1000 patients treated (95% CI: 300 r to 60). No data on urinary symptoms were reported. The association between diuretic use and severe adverse events was uncertain (RR 5.00, 95% CI 0.60-41.88, very low QoE); 4 more severe adverse events/1000 patients treated (95% CI: 0 fewer to 39 more). CONCLUSIONS The addition of diuretics to a normal or modified diet probably reduces the number of stone recurrences and may decrease the stone formation rate. It is uncertain whether diuretics increase the occurrence of severe adverse events. There were no studies investigating other outcomes or in children.
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Affiliation(s)
- Natalia Ferre
- Universitat Rovira i Virgili, School of Medicine, Pediatric Research Unit, Sant Llorenç 21, 43201 Reus, Spain
| | - Ester Parada
- Universitat Rovira i Virgili, School of Medicine, Pediatric Research Unit, Sant Llorenç 21, 43201 Reus, Spain; Department of Pediatrics, Hospital Universitari de Tarragona Joan XXIII, Dr. Mallafré Guasch 4, 43005 Tarragona, Spain
| | - Albert Balaguer
- Department of Pediatrics, Hospital Universitari General de Catalunya, Pere i Pons 1, 08195 Sant Cugat del Vallés, Barcelona, Spain; Universitat Internacional de Catalunya, Carrer de la Immaculada 22, 08017 Barcelona, Spain
| | - Albert Feliu
- Universitat Rovira i Virgili, School of Medicine, Pediatric Research Unit, Sant Llorenç 21, 43201 Reus, Spain; Department of Pediatrics, Hospital Universitari St Joan de Reus, Avinguda del Doctor Josep Laporte 2, 43204 Reus, Spain
| | - Marta Roqué-Figuls
- Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau), CIBER Epidemiología y Salud Pública (CIBERESP), Sant Quintí 77-79, 08041 Barcelona, Spain
| | - Juan Victor A Franco
- Argentine Cochrane Centre, Instituto Universitario Hospital Italiano, Potosí 4265, C1199 CABA Buenos Aires, Argentina
| | - Joaquín Escribano
- Universitat Rovira i Virgili, School of Medicine, Pediatric Research Unit, Sant Llorenç 21, 43201 Reus, Spain; Department of Pediatrics, Hospital Universitari St Joan de Reus, Avinguda del Doctor Josep Laporte 2, 43204 Reus, Spain.
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Metabolic risk factors in children with kidney stone disease: an update. Pediatr Nephrol 2020; 35:2107-2112. [PMID: 32564280 DOI: 10.1007/s00467-020-04660-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Revised: 06/02/2020] [Accepted: 06/09/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND The prevalence of kidney stones in children has significantly increased in the past few decades, with concomitant increased morbidity and healthcare costs worldwide. Assessing metabolic risk factors is essential for diagnosis and specific treatment. The objective of this retrospective study is to identify the epidemiological and clinical characteristics of children under 17 years of age, as well as the metabolic risk factors of nephrolithiasis. METHODS A total of 300 children with kidney stone disease were included to undergo several clinical tests using a standardized protocol. RESULTS The mean age was 11.2 years, and the male:female ratio was 1.15:1.0. Biochemical abnormalities were found in 89.3% of all cases. A single urine metabolic risk factor was present in 52.6% (n = 141) of the patients, and multiple risk factors were present in 36.7% (n = 106). Idiopathic hypercalciuria (alone or in combination) and hypocitraturia (alone or in combination) were the most frequent risk factors identified in 47.0% and 39.6% of these patients, respectively. Renal colic and/or unspecified abdominal pain were the most frequent forms of presentation (76.9%), followed by hematuria in 64.4% with 97.5% of stones located in the upper urinary tract. A positive family history in first-degree and second-degree relatives was found in 64.8% of boys and 61.8% of girls. CONCLUSIONS We conclude that specific urinary metabolic risk factors can be found in most children with kidney stones, with hypercalciuria and hypocitraturia being the most common diagnoses. Graphical abstract .
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Abstract
The causes of macroscopic and microscopic hematuria overlap; both are often caused by urinary tract infections or urethral/bladder irritation. Coexistent hypertension and proteinuria should prompt investigation for glomerular disease. The most common glomerulonephritis in children is postinfectious glomerulonephritis. In most patients, and especially with isolated microscopic hematuria, the diagnostic workup reveals no clear underlying cause. In those cases whereby a diagnosis is made, the most common causes of persistent microscopic hematuria are thin basement membrane nephropathy, immunoglobulin A nephropathy, or idiopathic hypercalciuria. Treatment and long-term prognosis varies with the underlying disease.
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Affiliation(s)
- Denver D Brown
- Pediatric Nephrology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, 3415 Bainbridge Avenue, Bronx, NY 10467, USA
| | - Kimberly J Reidy
- Pediatric Nephrology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, 3415 Bainbridge Avenue, Bronx, NY 10467, USA.
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Olschok K, Vester U, Lahme S, Kurth I, Eggermann T. No evidence for point mutations in the novel renal cystine transporter AGT1/SLC7A13 contributing to the etiology of cystinuria. BMC Nephrol 2018; 19:278. [PMID: 30342472 PMCID: PMC6196009 DOI: 10.1186/s12882-018-1080-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2017] [Accepted: 10/08/2018] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Cystinuria is caused by the defective renal reabsorption of cystine and dibasic amino acids, and results in cystine stone formation. So far, mutations in two genes have been identified as causative. The SLC3A1/rBAT gene encodes the heavy subunit of the heterodimeric rBAT-b0,+AT transporter, whereas the light chain is encoded by the SLC7A9/ b0,+AT gene. In nearly 85% of patients mutations in both genes are detectable, but a significant number of patients currently remains without a molecular diagnosis. Thus, the existence of a further cystinuria gene had been suggested, and the recently identified AGT1/SLC7A13 represents the long-postulated partner of rBAT and third cystinuria candidate gene. METHODS We screened a cohort of 17 cystinuria patients for SLC7A13 variants which were negative for SLC3A1 and SLC7A9 mutations. RESULTS Despite strong evidences for an involvement of SLC7A13 mutations in cystinuria, we could not confirm a relevant role of SLC7A13 for the disease. CONCLUSION With the exclusion of SLC7A13/AGT1 as the third cystinuria gene accounting for the SLC3A1 and SLC7A9 mutation negative cases, it becomes obvious that other genetic factors should be responsible for the cystinuria phenotype in nearly 15% of patients.
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Affiliation(s)
- Kathrin Olschok
- Institute of Human Genetics, University Hospital, Technical University RWTH Aachen, Pauwelsstr. 30, D-52074 Aachen, Germany
| | - Udo Vester
- Pediatric Hospital, University Hospital, University of Essen, Hufelandstr. 55, 45122 Essen, Germany
| | - Sven Lahme
- Department of Urology, St. Trudpert Hospital, Wilferdinger Str. 67, 75179 Pforzheim, Germany
| | - Ingo Kurth
- Institute of Human Genetics, University Hospital, Technical University RWTH Aachen, Pauwelsstr. 30, D-52074 Aachen, Germany
| | - Thomas Eggermann
- Institute of Human Genetics, University Hospital, Technical University RWTH Aachen, Pauwelsstr. 30, D-52074 Aachen, Germany
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Bazin D, Daudon M, André G, Weil R, Véron E, Matzen G. Therapy modifies cystine kidney stones at the macroscopic scale. Do such alterations exist at the mesoscopic and nanometre scale? J Appl Crystallogr 2014. [DOI: 10.1107/s1600576714004658] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
With an incidence of 1:7000 births, cystinuria, the most frequent cause of stone formation among genetic diseases, represents a major medical problem. Twenty-five cystine stones randomly selected from cystinuric patients were investigated. From a crystallographic point of view, cystine stones are composed of micrometre size crystallites, which are made up of an aggregation of nanocrystals. Through scanning electron microscopy, the morphology and size of the crystallites have been described, while the size of the nanocrystals was investigated by means of powder neutron diffraction. Powder neutron diffraction analysis and/or scanning electron microscopy examination of cystine stones provide evidence that usual alkalinization by sodium bicarbonate associated with high diuresis significantly reduces the size of both nanocrystals and crystallites, while for other treatments, including alkalinizing drugs and thiol derivatives, the data suggest mainly changes in the topology of crystallites. Alkalinization with sodium bicarbonate affects cystine kidney stones at the mesoscopic and nanoscopic scales, while other medical treatments only alter their surface. Such an approach may help to assess the interaction between drugs and cystine stones in cystinuric patients.
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Escribano J, Balaguer A, Roqué i Figuls M, Feliu A, Ferre N, Cochrane Kidney and Transplant Group. Dietary interventions for preventing complications in idiopathic hypercalciuria. Cochrane Database Syst Rev 2014; 2014:CD006022. [PMID: 24519664 PMCID: PMC10660327 DOI: 10.1002/14651858.cd006022.pub4] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
BACKGROUND Idiopathic hypercalciuria is an inherited metabolic abnormality that is characterised by excessive amounts of calcium excreted in the urine by people whose calcium serum levels are normal. Morbidity associated with idiopathic hypercalciuria is chiefly related to kidney stone disease and bone demineralisation leading to osteopenia and osteoporosis. Idiopathic hypercalciuria contributes to kidney stone disease at all life stages; people with the condition are prone to developing oxalate and calcium phosphate kidney stones. In some cases, crystallised calcium can be deposited in the renal interstitium, causing increased calcium levels in the kidneys. In children, idiopathic hypercalciuria can cause a range of comorbidities including recurrent macroscopic or microscopic haematuria, frequency dysuria syndrome, urinary tract infections and abdominal and lumbar pain. Various dietary interventions have been described that aim to decrease urinary calcium levels or urinary crystallisation. OBJECTIVES Our objectives were to assess the efficacy, effectiveness and safety of dietary interventions for preventing complications in idiopathic hypercalciuria (urolithiasis and osteopenia) in adults and children, and to assess the benefits of dietary interventions in decreasing urological symptomatology in children with idiopathic hypercalciuria. SEARCH METHODS We searched the Cochrane Renal Group's Specialised Register (23 April 2013) through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE and EMBASE. SELECTION CRITERIA We included all randomised controlled trials (RCTs) and quasi-RCTs that investigated dietary interventions aimed at preventing complications of idiopathic hypercalciuria, compared with placebo, no intervention, or other dietary interventions regardless of route of administration, dose or amount. DATA COLLECTION AND ANALYSIS Studies were assessed for inclusion and data extracted using a standardised data extraction form. We calculated risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, both with 95% confidence intervals (CI). MAIN RESULTS We included five studies (379 adult participants) that investigated a range of interventions. Lack of similarity among interventions investigated meant that data could not be pooled. Overall, study methodology was not adequately reported in any of the included studies. There was a high risk of bias associated with blinding (although it seems unlikely that outcomes measures were unduly influenced by lack of intervention blinding), random sequence generation and allocation methodologies were unclear in most studies, but selective reporting bias was assessed as low.One study (120 participants) compared a low calcium diet with a normal calcium, low protein, low salt diet for five years. There was a significant decrease in numbers of new stone recurrences in those treated with the normal calcium, low protein, low salt diet (RR 0.77, 95% CI 0.61 to 0.98). This diet also led to a significant decrease in oxaluria (MD 78.00 µmol/d, 95% CI 26.48 to 129.52) and the calcium oxalate relative supersaturation index (MD 1.20 95% CI 0.21 to 2.19).One study (210 participants) compared a low salt, normal calcium diet with a broad diet for three months. The low salt, normal calcium diet decreased urinary calcium (MD -45.00 mg/d, 95% CI -74.83 to -15.17) and oxalate excretion (MD -4.00 mg/d, 95% CI -6.44 to -1.56).A small study (17 participants) compared the effect of dietary fibre as part of a low calcium, low oxalate diet over three weeks, and found that although calciuria levels decreased, oxaluria increased. Phyllanthus niruri plant substrate intake was investigated in a small subgroup with hypercalciuria (20 participants); there was no significant effect on calciuria levels occurred after three months of treatment.A small cross-over study (12 participants) evaluating the changes in urinary supersaturation indices among patients who consumed calcium-fortified orange juice or milk for one month found no benefits for participants.None of the studies reported any significant adverse effects associated with the interventions. AUTHORS' CONCLUSIONS Long-term adherence (five years) to diets that feature normal levels of calcium, low protein and low salt may reduce numbers of stone recurrences, decrease oxaluria and calcium oxalate relative supersaturation indexes in people with idiopathic hypercalciuria who experience recurrent kidney stones. Adherence to a low salt, normal calcium level diet for some months can reduce calciuria and oxaluria. However, the other dietary interventions examined did not demonstrate evidence of significant beneficial effects.No studies were found investigating the effect of dietary recommendations on other clinical complications or asymptomatic idiopathic hypercalciuria.
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Affiliation(s)
- Joaquin Escribano
- Hospital Universitari St Joan de ReusDepartment of PediatricsUniversitat Rovira i VirgiliSt Joan s/nReusCataloniaSpain43201
| | - Albert Balaguer
- Universitat Internacional de CatalunyaDepartment of Pediatrics. Hospital General de Catalunya.C/ Pedro I Pons, 1Sant Cugat de VallésBarcelonaCATALONIASpain08195
| | - Marta Roqué i Figuls
- CIBER Epidemiología y Salud Pública (CIBERESP)Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau)Sant Antoni Maria Claret 171Edifici Casa de ConvalescènciaBarcelonaCatalunyaSpain08041
| | - Albert Feliu
- Hospital Universitari St Joan de ReusDepartment of PediatricsUniversitat Rovira i VirgiliSt Joan s/nReusCataloniaSpain43201
| | - Natalia Ferre
- Universitat Rovira i VirgiliPediatric Research Unit, School of MedicineSant Lloreç, 21TarragonaSpain43201
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Abstract
Childhood urolithiasis is an evolving condition with an increasing incidence and prevalence over the last 2 decades. Over that time the underlying cause has shifted from predominantly infectious to metabolic in nature. This review describes the pathophysiology, underlying metabolic abnormalities, clinical presentation, evaluation, and management of childhood urolithiasis. A comprehensive metabolic evaluation is essential for all children with renal calculi, given the high rate of recurrence and the importance of excluding inherited progressive conditions.
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Affiliation(s)
- Lawrence Copelovitch
- Division of Nephrology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
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Elkoushy MA, Andonian S. Characterization of patients with heterozygous cystinuria. Urology 2012; 80:795-9. [PMID: 22854136 DOI: 10.1016/j.urology.2012.04.062] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2011] [Revised: 03/22/2012] [Accepted: 04/20/2012] [Indexed: 02/02/2023]
Abstract
OBJECTIVE To characterize a contemporary cohort of patients with heterozygous (TZ) cystinuria and compare them with a concurrent cohort of patients with homozygous (MZ) cystinuria. METHODS A retrospective review of prospectively collected data was performed for 42 consecutive patients presenting with a positive cyanide-nitroprusside test from September 2009 to September 2011. Clinical data were collected, including the findings from a detailed metabolic stone workup that included two 24-hour urine collections with quantitative cystine. The patients were divided into 2 groups: those with TZ (30-400 mg/d) and those with MZ (>400 mg/d) cystinuria. RESULTS One patient was excluded because the cystine excretion was within the normal range (<30 mg/d), 35 (83.3%) and 6 (14.3%) had TZ and MZ cystinuria, respectively. Compared with those with TZ cystinuria, those with MZ cystinuria were significantly younger at the first stone episode (median 48 years, range 14-67, vs 17, range 6-44, P = .002), more were female (20% vs 66.7%; P = .03), and more patients had bilateral stones (8.6% vs 50%; P = .03). Finally, the patients with MZ cystinuria had more stone episodes than those with TZ cystinuria (3 vs 1; P = .04). From the detailed metabolic stone evaluation, the incidence of hyperuricemia was significantly greater in the MZ patients (17.1% vs 66.7%; P = .02). Although all the MZ patients developed pure cystine stones, 18 (51.4%), 7 (20.0%), and 3 (8.6%) of the TZ patients developed calcium oxalate, uric acid, and cystine stones, respectively (P < .001). In the TZ group, 11 patients (31.4%) had false-negative results on subsequent cyanide-nitroprusside testing. CONCLUSION Significant differences were found between the patients with TZ and MZ cystinuria in terms of age at the first stone episode, male/female ratio, incidence of hyperuricemia, and stone composition. The clinical significance remains to be elucidated.
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Affiliation(s)
- Mohamed A Elkoushy
- Division of Urology, Department of Surgery, McGill University Health Centre, McGill University, Montreal, Quebec, Canada
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Moreira Guimarães Penido MG, de Sousa Tavares M. Bone disease in pediatric idiopathic hypercalciuria. World J Nephrol 2012; 1:54-62. [PMID: 24175242 PMCID: PMC3782196 DOI: 10.5527/wjn.v1.i2.54] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2011] [Revised: 11/11/2011] [Accepted: 02/10/2012] [Indexed: 02/06/2023] Open
Abstract
Idiopathic hypercalciuria (IH) is the leading metabolic risk factor for urolithiasis and affects all age groups without gender or race predominance. IH has a high morbidity with or without lithiasis and reduced bone mineral density (BMD), as described previously in pediatric patients as well as in adults. The pathogenesis of IH is complex and not completely understood, given that urinary excretion of calcium is the end result of an interplay between three organs (gut, bone and kidney), which is further orchestrated by hormones, such as 1,25 dihydroxyvitamin D, parathyroid hormone, calcitonin and fosfatonins (i.e., fibroblast growth-factor-23). Usually, a primary defect in one organ induces compensatory mechanisms in the remaining two organs, such as increased absorption of calcium in the gut secondary to a primary renal loss. Thus, IH is a systemic abnormality of calcium homeostasis with changes in cellular transport of this ion in intestines, kidneys and bones. Reduced BMD has been demonstrated in pediatric patients diagnosed with IH. However, the precise mechanisms of bone loss or failure of adequate bone mass gain are still unknown. The largest accumulation of bone mass occurs during childhood and adolescence, peaking at the end of the second decade of life. This accumulation should occur without interference to achieve the peak of optimal bone mass. Any interference may be a risk factor for the reduction of bone mass with increased risk of fractures in adulthood. This review will address the pathogenesis of IH and its consequence in bone mass.
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Affiliation(s)
- Maria Goretti Moreira Guimarães Penido
- Maria Goretti Moreira Guimarães Penido, Marcelo de Sousa Tavares, Department of Pediatrics, Pediatric Nephrology Unit, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Belo Horizonte, CEP 30130100, Minas Gerais, Brazil
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Eggermann T, Venghaus A, Zerres K. Cystinuria: an inborn cause of urolithiasis. Orphanet J Rare Dis 2012; 7:19. [PMID: 22480232 PMCID: PMC3464901 DOI: 10.1186/1750-1172-7-19] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2011] [Accepted: 04/05/2012] [Indexed: 12/04/2022] Open
Abstract
Cystinuria (OMIM 220100) is an inborn congenital disorder characterised by a defective cystine metabolism resulting in the formation of cystine stones. Among the heterogeneous group of kidney stone diseases, cystinuria is the only disorder which is exclusively caused by gene mutations. So far, two genes responsible for cystinuria have been identified: SLC3A1 (chromosome 2p21) encodes the heavy subunit rBAT of a renal b0,+ transporter while SLC7A9 (chromosome 19q12) encodes its interacting light subunit b0,+AT. Mutations in SLC3A1 are generally associated with an autosomal-recessive mode of inheritance whereas SLC7A9 variants result in a broad clinical variability even within the same family. The detection rate for mutations in these genes is larger than 85%, but it is influenced by the ethnic origin of a patient and the pathophysiological significance of the mutations. In addition to isolated cystinuria, patients suffering from the hypotonia-cystinuria syndrome have been reported carrying deletions including at least the SLC3A1 and the PREPL genes in 2p21. By extensive molecular screening studies in large cohort of patients a broad spectrum of mutations could be identified, several of these variants were functionally analysed and thereby allowed insights in the pathology of the disease as well as in the renal trafficking of cystine and the dibasic amino acids. In our review we will summarize the current knowledge on the physiological and the genetic basis of cystinuria as an inborn cause of kidney stones, and the application of this knowledge in genetic testing strategies.
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Affiliation(s)
- Thomas Eggermann
- Institute of Human Genetics, University Hospital, RWTH Aachen, Pauwelsstr, 30, Aachen, D-52074, Germany.
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Metabolic Stone Disease in Children. Urolithiasis 2012. [DOI: 10.1007/978-1-4471-4387-1_78] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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15
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Aydogdu O, Burgu B, Gucuk A, Suer E, Soygur T. Effectiveness of Doxazosin in Treatment of Distal Ureteral Stones in Children. J Urol 2009; 182:2880-4. [DOI: 10.1016/j.juro.2009.08.061] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2009] [Indexed: 10/20/2022]
Affiliation(s)
- Ozgu Aydogdu
- Pediatric Urology Unit, Department of Urology, Ankara University Faculty of Medicine, Ankara, Turkey
| | - Berk Burgu
- Pediatric Urology Unit, Department of Urology, Ankara University Faculty of Medicine, Ankara, Turkey
| | - Adnan Gucuk
- Department of Urology, Yildirim Beyazit Hospital, Ankara, Turkey
| | - Evren Suer
- Pediatric Urology Unit, Department of Urology, Ankara University Faculty of Medicine, Ankara, Turkey
| | - Tarkan Soygur
- Pediatric Urology Unit, Department of Urology, Ankara University Faculty of Medicine, Ankara, Turkey
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Porowski T, Konstantynowicz J, Zoch-Zwierz W, Kirejczyk JK, Taranta-Janusz K, Korzeniecka-Kozerska A. Spontaneous urinary calcium oxalate crystallization in hypercalciuric children. Pediatr Nephrol 2009; 24:1705-10. [PMID: 19350280 DOI: 10.1007/s00467-009-1171-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2008] [Revised: 02/25/2009] [Accepted: 02/27/2009] [Indexed: 11/25/2022]
Abstract
Idiopathic hypercalciuria is the most important predisposing risk factor for calcium oxalate (CaOx) renal stone formation. We assessed the associations between spontaneous CaOx crystallization based on the Bonn Risk Index (BRI), urinary pH, calciuria, oxaluria, and citraturia in 140 Caucasian patients with hypercalciuria, aged 4-17 years, and compared the findings with those in 210 normocalciuric controls. Of the 140 hypercalciuric patients, 58 had renal stones, and 82 had recurrent erythrocyturia, renal colic, or urinary obstructive symptoms-but without stones. Urinary ionized calcium ([Ca(2+)]) levels were measured using a selective electrode, while the onset of crystallization was determined using a photometer and titration with 40 mmol/L ammonium oxalate (Ox(2-)). The calculation of the BRI was based on the [Ca(2+)]:Ox(2-) ratio. The BRI values were 12-fold higher in hypercalciuric children than in healthy controls, but no differences were found in the BRI between subjects with urinary stones and those with urolithiasis-like symptoms. An increased BRI suggested an association with hypercalciuria, lower urinary pH, hypocitraturia, and hypooxaluria. These data indicate that hypercalciuria is an important factor associated with increased urinary CaOx crystallization, although the causal pathways need further investigation. Determination of the BRI in children with hypercalciuria may improve the risk assessment of kidney stones.
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Affiliation(s)
- Tadeusz Porowski
- Department of Pediatrics and Nephrology, Children's Hospital, Medical University of Bialystok, 17 Waszyngtona St., 15-274, Bialystok, Poland.
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Spivacow FR, Negri AL, del Valle EE, Calviño I, Zanchetta JR. Clinical and metabolic risk factor evaluation in young adults with kidney stones. Int Urol Nephrol 2009; 42:471-5. [PMID: 19653114 DOI: 10.1007/s11255-009-9623-0] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2009] [Accepted: 07/15/2009] [Indexed: 11/26/2022]
Abstract
INTRODUCTION The most frequent urine metabolic risk factor in adults is idiopathic hypercalciuria while in children is hypocitraturia. If there is really a change of metabolic abnormalities with age it would be interesting to study risk factors in the intermediate population: young adults. OBJECTIVE We evaluated metabolic risk factors, clinical presentation and family history of stone formers between 17 and 27 years old. METHODS A total of 160 patients (87 males and 73 females) were studied with a standard protocol. RESULTS A single urine metabolic risk factor was present in 64% of the patients, and multiple risk factors were present in 27% of them. No metabolic abnormalities were found in the remaining 9%. The most common urine risk factor was idiopathic hypercalciuria (alone or in combination), which was identified in 42.5% followed by hypocitraturia (alone or in combination) found in 32.9% of the patients. In the subgroup of patients of 17-20 years (n = 75; mean age of 18.8 + or - 1.0 years), hypocitraturia (alone or in combination) was as frequent as idiopathic hypercalciuria (alone or in combination), which was identified in 38% (n = 30) and 36.7% (n = 29), respectively. The most frequent form of presentation was renal colic (72%). A positive family history of stone disease in first degree and second-degree relatives was found in 32.9 and 34.1%, respectively. CONCLUSIONS Metabolic abnormalities were found in 91% of young adults with renal lithiasis, similar to our adult series. Hypercalciuria was the most frequent metabolic abnormality found. Yet, hypocitraturia (alone or in combination) was very frequent, and in the subgroup of patients of 17-20 years, it was as frequent as idiopathic hypercalciuria, similar to what we found in children.
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Affiliation(s)
- Francisco R Spivacow
- Instituto de Investigaciones Metabólicas, Universidad del Salvador, Libertad 836 1 piso, Buenos Aires 1012, Argentina
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Srivastava T, Winston MJ, Auron A, Alon US. Urine calcium/citrate ratio in children with hypercalciuric stones. Pediatr Res 2009; 66:85-90. [PMID: 19287339 DOI: 10.1203/pdr.0b013e3181a2939e] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Hypercalciuria is a common cause for stone formation in children. The aim was to delineate the role of urinary citrate in hypercalciuric children for protection against calcium stone formation. We evaluated random urine calcium, citrate, and creatinine in 149 controls, 78 hypercalciuric nonstone formers, and 34 hypercalciuric children with stone. Urine citrate/creatinine was highest in hypercalciuric nonstone formers 899 +/- 351 compared with controls 711 +/- 328 and stone formers 595 +/- 289 (p < 0.01 vs. both). Calcium/creatinine ratio was similar in hypercalciuric stone and nonstone formers, but significantly higher than controls. Consequently, urine calcium/citrate ratio (mg/mg) increased from control 0.17 +/- 0.17 to 0.41 +/- 0.23 (p < 0.001) in hypercalciuric nonstone formers, and to 0.65 +/- 0.46 in stone formers (p < 0.001 compared with other groups). Area under receiver operating characteristic curve combined with multilevel risk analyses found calcium/citrate ratio of 0.326 to provide good discrimination between control and stone formers. We found 5th percentile for random urine citrate/creatinine ratio in school-aged children to be 176 mg/g, elevated urinary citrate excretion in hypercalciuric children to be protective against stone formation, and urine calcium/citrate ratio to be a good indicator for risk of stone formation. Whether intervention in hypercalciuric children to lower urine calcium/citrate <0.326 will provide protection against stone formation needs to be studied.
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Affiliation(s)
- Tarak Srivastava
- Bone and Mineral Disorder Clinic, University of Missouri at Kansas City, 2401 Gillham Road, Kansas City, MO 64108, USA.
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Escribano J, Balaguer A, Pagone F, Feliu A, Roqué I Figuls M. Pharmacological interventions for preventing complications in idiopathic hypercalciuria. Cochrane Database Syst Rev 2009; 2009:CD004754. [PMID: 19160242 PMCID: PMC7053686 DOI: 10.1002/14651858.cd004754.pub2] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Idiopathic hypercalciuria is an inherited metabolic abnormality characterised by excessive amounts of calcium excreted into the urine in patients with normal serum levels of calcium. The morbidity of hypercalciuria is related to kidney stone disease and bone demineralization. In children, hypercalciuria can cause recurrent haematuria, frequency-dysuria syndrome, urinary tract infection and abdominal and lumbar pain. Several pharmacological treatments have been described that can decrease the levels of urinary calcium or its index of urinary crystallization. OBJECTIVES To assess the benefits and harms of pharmacological interventions for preventing complications and decreasing urological symptoms in patients with idiopathic hypercalciuria. SEARCH STRATEGY We searched MEDLINE, EMBASE, the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), handsearched relevant conference proceedings and reference lists of articles. SELECTION CRITERIA All randomised controlled trials (RCTs) and quasi-RCTS that compared any pharmacological intervention for preventing complications in idiopathic hypercalciuria, with placebo, other pharmacological intervention or a different administration mode or dose of the same treatment given for a minimum duration of four months and had a follow-up period of at least six months. DATA COLLECTION AND ANALYSIS Four authors assessed the studies for inclusion and extracted the data. Disagreements were resolved through discussion. Results were expressed as risk ratios (RR) with 95% confidence intervals (CI) or mean difference (MD). MAIN RESULTS Five studies (316 adult patients) were included. Four compared thiazides with standard treatment (periodic clinical follow-up and increased water intake) or specific dietary recommendations and one analysed the effect of thiazide plus a neutral potassium salt. There was a significant decrease in the number of new stone recurrences in those treated with thiazides (RR 1.61, 95% CI 1.33 to 1.96), although the follow-up periods varied. The stone formation rate also showed a statistically significant decrease in the patients treated with diuretics (MD -0.18, 95% CI -0.30 to -0.06). Thiazides plus potassium salts significantly decreased calciuria and vitamin D levels. AUTHORS' CONCLUSIONS There is some evidence that in patients with idiopathic hypercalciuria and recurrent stones, the addition of thiazides to a normal or modified diet for short to long periods (five months to three years) reduced the number of stone recurrences and decreased the stone formation rate. Thiazides and neutral potassium phosphate decreased calciuria in symptomatic patients with idiopathic hypercalciuria. There were no studies investigating the effect of pharmacological treatment on other clinical complications or asymptomatic idiopathic hypercalciuria.
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Affiliation(s)
- Joaquin Escribano
- Department of Pediatrics, Hospital Universitari St Joan de Reus, Universitat Rovira i Virgili, St Joan s/n, Reus, Catalonia, Spain, 43201.
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Metabolic risk factors in children with kidney stone disease. Pediatr Nephrol 2008; 23:1129-33. [PMID: 18324422 DOI: 10.1007/s00467-008-0769-2] [Citation(s) in RCA: 99] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2007] [Revised: 01/03/2008] [Accepted: 01/08/2008] [Indexed: 12/20/2022]
Abstract
The evaluation of metabolic risk factor in children with renal stone disease is the basis of medical treatment aimed at preventing recurrent stone events and the growth of preexisting calculi. In this retrospective study, we evaluated the metabolic risk factors and clinical and family histories of 90 children with kidney stone disease who had been referred to our institution and subjected to clinical tests using a standardized protocol. The mean age of our pediatric patients was 10.7 years, and the male:female ratio was 1.14:1.0. Biochemical abnormalities were found in 84.4% of all cases. A single urine metabolic risk factor was present in 52.2% (n = 47) of the patients, and multiple risk factors were present in the remaining 31.1% (n = 28). Idiopathic hypercalciuria (alone or in combination) and hypocitraturia (alone or in combination) were the most frequent risk factors identified in 40 and 37.8% of these patients, respectively. Renal colic or unspecified abdominal pain were the most frequent forms of presentation (76.9%), with 97.5% of stones located in the upper urinary tract. In most patients, stone disease was confirmed by renal ultrasonography (77%). A positive family history in first-degree and second-degree relatives was found in 46.2 and 32.5% of the cases, respectively. We conclude that specific urine metabolic risk factors are found in most children with kidney stones and that hypocitraturia is as frequent as hypercalciuria. Very often there is a positive family history of renal stone disease in first- and second-degree relatives.
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Tanzer F, Ozgur A, Bardakci F. Type I cystinuria and its genetic basis in a population of Turkish school children. Int J Urol 2008; 14:914-7. [PMID: 17880288 DOI: 10.1111/j.1442-2042.2007.01852.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
OBJECTIVES Cystinuria is a common inherited disorder characterized by an abnormal urinary excretion of cystine and dibasic amino acids resulting in nephrolithiasis. The SLC3A1 gene, which encodes a dibasic amino acid transporter protein, is involved in the pathogenesis of cystinuria. In the present study we aimed to investigate the prevalence of cystinuria among children in Sivas province (Central Anatolia, Turkey) and to study M467T and M467K mutations and 231T/A polymorphism in patients with cystinuria. METHODS A total of 8500 children were screened for cystinuria. The cyanide-nitroprusside test was applied to urine samples of all children. Children having a positive cyanide-nitroprusside test were further analyzed. M467T and M467K mutations (exon 8) and 231T/A polymorphism (exon 1) in the SCL3A1 gene were studied using a restriction fragment length polymorphism (RFLP) assay. RESULTS We have found that the prevalence of cystinuria (11 cystinuric patients) is 1/772 in our population. Results of mutation analysis in the patients with cystinuria showed that M467T was the only mutation that was found in six cystinuric patients. One patient was homozygous and five were heterozygous for this mutation. CONCLUSIONS The frequency of cystinuria in Sivas Province is the highest among the other populations studied to date. The frequency of M467T mutation is relatively higher than those reported for most populations. High frequency of cystinuria in this region could be due to consanguineous marriages.
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Affiliation(s)
- Fatos Tanzer
- Department of Pediatrics, Faculty of Medicine, Cumhuriyet University, Sivas, Turkey.
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Romero Otero J, Gómez Fraile A, Feltes Ochoa JA, Fernández I, López Vázquez F, Aransay Bramtot A. [The lithiasis in the upper urinary tract in children: endourological treatment]. Actas Urol Esp 2007; 31:532-8; discussion 538-40. [PMID: 17711173 DOI: 10.1016/s0210-4806(07)73678-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
INTRODUCTION Urolithiasis in the pediatric age is a growing problem. In the developed world they are of calcium oxalate and in the upper urinary tract. It is very similar to the presentation of lithiasis in adults, so we have to make an effort to apply the experience in this age to the children. The shock wave lithotripsy is admitted as the first treatment for this pathology in the pediatric population already. The endourological approach must be use as a common approach in this group. We present our technique and experience. MATERIAL AND METHODS A retrospective, descriptive study of the children diagnosed of lithiasis in the upper urinary tract that were treated by an endourological technique in our centre between January 1992 and January 2005. We gathered data on: 1.) Preoperative: age, sex, clinical manifestations, size (mm) and position of the lithiasis (we divided the upper urinary tract in: renal, proximal third, medial third and distal third) 2.) Operative variable: endourological technique: percutaneus neprolithotomy or ureteroscopy. Reconversion to open surgery. 3.) Postoperative variables: time since surgery, complications and the current state of the patient (ultrasonography and renal function). RESULTS Seven children, 4 boys and 2 girls with an age range of 2,5 to 14 years, underwent operation using an endourological technique. Lumboabdominal pain was the main clinical manifestation (4/7). The lithiasis size was 4-7mm, with the exception of a staghorn calculis. The calculis were: 5 ureteral proximal, 1 ureteral distal and one in the kidney (staghound stone). We performed one percutaneus neprolithotomy for the staghorn calculi. We removed completly the stone and had no complications. The 6 other procedures were ureteroscopies. In 3 of them we removed the calculi (4/7 success rate of 57%). The rest procedures we needed to transform in open surgery. With a following time of 1-13 years all of them are asymptomatic, and with ultrasonography and renal function in the normal limits. We did see no complications. CONCLUSION The endourological treatment for urolithiasis in pediatric patients is possible but must be individualized in each case. With the development of new endourological material and more surgical experience this technique will be to the reach of the most of the urologists.
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Affiliation(s)
- J Romero Otero
- Sección de Urología Pediátrica, Hospital Universitario 12 de Octubre, Madrid.
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Lambrecht FY, Kavukçu S, Kasap B, Soylu A, Yücesoy M, Türkmen M, Esen N, Unak P. The role of calcium utilization of intestinal flora in urinary calcium excretion. J Ren Nutr 2007; 17:148-150. [PMID: 17321955 DOI: 10.1053/j.jrn.2006.07.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2006] [Indexed: 02/08/2023] Open
Abstract
OBJECTIVE We aimed to evaluate whether Ca(+2) utilization of intestinal flora (IF) has an effect on urinary excretion of Ca(+2) (UCaE) levels. MATERIALS AND METHODS Fecal samples (0.1 g/mL) of children who underwent UCaE examination in the past year were implanted in broths. Labeled (45)Ca (5 muL) was added to the samples and incubated. From these samples, a 200-muL quantity was filtrated with a 0.45-micrometer membrane and was rinsed in 200 muL pure water. (45)Ca activity in the membrane was measured and defined as percent activity per bacteria ((45)Ca(act) %/CFU). Levels of aerobic and anaerobic (45)Ca(act) %/CFU and their correlations with UCaE were compared between hypercalciuric (Group I) and normocalciuric (Group II) patients. RESULTS Levels of (45)Ca %/CFU were similar between groups (P > .05). Aerobic and anaerobic (45)Ca(act)%/CFU levels were not significantly correlated to UCaE, either in normocalciuric (P = .079, r = -0.503; P = .260, r = -0.420, stray mart respectively) or in hypercalciuric children (P = .509, r = 0.223; P = .623, r = -0.257, respectively). CONCLUSION Similar (45)Ca(act)%/CFU levels in the 2 groups imply that calcium utilization of IF does not have a distinct effect on UCaE.
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Affiliation(s)
- Fatma Yurt Lambrecht
- Department of Nuclear Applications, Ege University Institute of Nuclear Sciences, Izmir, Turkey
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Srivastava T, Alon US. Pathophysiology of hypercalciuria in children. Pediatr Nephrol 2007; 22:1659-73. [PMID: 17464515 PMCID: PMC6904412 DOI: 10.1007/s00467-007-0482-6] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2007] [Revised: 03/11/2007] [Accepted: 03/12/2007] [Indexed: 12/17/2022]
Abstract
Urinary excretion of calcium is the result of a complex interplay between three organs-namely, the gastrointestinal tract, bone, and kidney-which is finely orchestrated by multiple hormones. Hypercalciuria is believed to be a polygenic trait and is influenced significantly by diet. This paper briefly reviews calcium handling by the renal tubule in normal and in hereditary disorders as it relates to the pathophysiology of hypercalciuria. The effects of dietary sodium, potassium, protein, calcium, and phosphate on calcium excretion, and the association of hypercalciuria with bone homeostasis is discussed, leading to recommendations on means to address excessive urinary calcium excretion.
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Affiliation(s)
- Tarak Srivastava
- Section of Nephrology, Bone and Mineral Disorder Clinic, The Children’s Mercy Hospital and Clinics, University of Missouri, 2401 Gillham Road, Kansas City, MO 64108 USA
| | - Uri S. Alon
- Section of Nephrology, Bone and Mineral Disorder Clinic, The Children’s Mercy Hospital and Clinics, University of Missouri, 2401 Gillham Road, Kansas City, MO 64108 USA
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Brauers E, Hozyasz K, Golabek B, Slowik M, Schmidt C, Vester U, Zerres K, Eggermann T. Identification of novel cystinuria mutations in pediatric patients. J Pediatr Urol 2006; 2:575-8. [PMID: 18947684 DOI: 10.1016/j.jpurol.2005.11.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2005] [Accepted: 11/22/2005] [Indexed: 10/25/2022]
Abstract
OBJECTIVE Cystinuria is a common inherited disorder of renal reabsorption of cystine and the dibasic amino acids. So far, mutations in two genes (SLC3A1 and SLC7A9) have been identified in cystinuria patients. Molecular searches for cystinuria mutations show that their distribution depends on the ethnic origin of the patients, but have not allowed the detection of 100% of variants. Pediatric patients representing a severe form of the disease appear to carry other mutations than those patients referred from urological centers. We analysed patients with an age of manifestation less than 15 years for mutations in the two cystinuria genes. PATIENTS AND METHODS We screened 17 patients for mutations in SLC3A1 and SLC7A9, 15 of whom were younger than 16 years at first stone formation. The search for mutations used PCR-based standard techniques, and was focused on point mutations and larger deletions and duplications in both genes. RESULTS Apart from detection of mutations in approximately 70% of patients but identification of only 53% of alleles, we detected three novel mutations as well as three new polymorphisms. CONCLUSION The detection rate in young cystinuria patients is lower than that in older patients, and there is a different pattern of variants. There is evidence for other (probably genetic) factors being involved in the pathophysiology of cystinuria.
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Affiliation(s)
- Eva Brauers
- Institute of Human Genetics, University Hospital, RWTH, Pauwelsstr. 30, D-52074 Aachen, Germany
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Schell-Feith EA, Moerdijk A, van Zwieten PHT, Zonderland HM, Holscher HC, Kist-van Holthe J, van der Heijden BJ. Does citrate prevent nephrocalcinosis in preterm neonates? Pediatr Nephrol 2006; 21:1830-6. [PMID: 17039333 DOI: 10.1007/s00467-006-0274-4] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2006] [Revised: 06/21/2006] [Accepted: 07/06/2006] [Indexed: 11/25/2022]
Abstract
Nephrocalcinosis (NC) occurs frequently in preterm neonates. A high U-calcium/citrate is one of the contributing factors to the development of NC. In stone-forming children and adults citrate supplementation is a successful preventive therapy. In this randomized controlled trial the effect of citrate therapy was studied on the development of NC in preterm neonates with a gestational age <32 weeks. Thirty-eight preterm neonates (mean gestational age 29.8 weeks (SD 1.6), mean birth weight 1,300 g (SD 351) were treated with sodium citrate (0.52 mmol/kg/day in four doses) from day 8 of life until at term and 36 preterm neonates (mean gestational age 29.6 weeks (SD 1.6), mean birth weight 1,282 g (SD 256) were not treated. U-calcium, U-creatinine, U-citrate and U-pH were measured at day 7, 14, 21, 28 of life and at term. Renal ultrasonography (US) was performed at term. U-citrate/creatinine and U-pH were significantly higher and U-calcium/citrate was significantly lower in the citrate group at day 14, 21 and 28 compared with the control group (P<0.05). Complications of citrate administration were not encountered, however the incidence of NC was not significantly different in the treated (34%) compared with the control group (44%), P=0.37. Preterm neonates treated with citrate in the first months of life have higher U-citrate/creatinine and lower U-calcium/citrate compared with controls. Sodium citrate therapy in a dosage of 0.52 mmol/kg/day is safe but does not prevent NC. Whether a higher dose or potassium citrate decreases the incidence of NC should be evaluated in further studies.
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Korkes F, Segal AB, Heilberg IP, Cattini H, Kessler C, Santili C. Immobilization and hypercalciuria in children. Pediatr Nephrol 2006; 21:1157-60. [PMID: 16819644 DOI: 10.1007/s00467-006-0157-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2005] [Revised: 03/06/2006] [Accepted: 03/07/2006] [Indexed: 11/28/2022]
Abstract
Intermediate-term immobilization may lead to an increase in serum and urinary calcium. In order to test this hypothesis, we evaluated 46 children, 21 with Legg-Calvé-Perthes disease (LCP; 7.2+/-1.8 years old) and 25 with developmental dysplasia of the hip joint (DDH; 10+/-5 months of age), submitted to immobilization for up to 16 weeks. These two conditions require intermediate-term immobilization as treatment modality, and no studies evaluating calcium metabolism in these groups of patients have been conducted. In LCP patients, blood and 24-h urine samples were obtained before the beginning of treatment and after 1, 6, 8, 14 and 16 weeks of immobilization, while in DDH patients, blood and spot urine samples were collected before treatment and after 6 and 14 weeks of treatment. Urinary calcium, creatinine, potassium and sodium as well as serum calcium, phosphorus, parathyroid hormone, creatinine and alkaline phosphatase were determined in those samples. Renal ultrasound was performed before and after treatment. A mean increase of 2.3 times baseline values of urinary calcium was observed in 40% of previously normocalciuric LCP patients after only 1 week of immobilization. Among the DDH children, who had never previously ambulated, there was no significant variation in the urinary calcium excretion. None of the serum parameters changed in either group throughout the study. Urinary stones were not evidenced by renal ultrasound. Therefore, the present data suggested that intermediate-term immobilization led to a transient increase in urinary calcium in 40% of LCP patients. Complications such as urinary stones were not observed. In conclusion, this modality of treatment does not impose an increased risk of urinary stone formation in LCP and DDH patients.
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Affiliation(s)
- Fernando Korkes
- Department of Urology, Medical Sciences School of Santa Casa of São Paulo, São Paulo, Brazil.
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Abstract
Nephrolithiasis is responsible for 1 in 1000 to 1 in 7600 pediatric hospital admissions annually throughout the United States. Seventy-five percent of children with nephrolithiasis have an identifiable predisposition to stone formation. This article reviews the different causes and disease states associated with nephrolithiasis in the pediatric population. The initial evaluation and the metabolic evaluation of children with nephrolithiasis are reviewed. Treatment modalities for the different stone types are also described.
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Affiliation(s)
- Julie A Nicoletta
- Division of Pediatric Nephrology, Department of Pediatrics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14624, USA.
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Sarica K. Pediatric urolithiasis: etiology, specific pathogenesis and medical treatment. ACTA ACUST UNITED AC 2006; 34:96-101. [PMID: 16432692 DOI: 10.1007/s00240-005-0018-0] [Citation(s) in RCA: 66] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/12/2005] [Indexed: 11/24/2022]
Abstract
Pediatric urolithiasis is an endemic disease in certain parts of the world, namely Turkey and the Far East. As a recurrent pathology which may reveal functional as well and morphologic changes in the urinary tract, environmental factors together with urogenital abnormalities should be evaluated thoroughly in each patient. The aims of management should be complete clearance of stones, treatment of urinary tract infections, preservation of renal function and prevention of stone recurrence. In addition to certain minimally invasive stone removal procedures, treatment of pediatric urolithiasis requires a detailed metabolic evaluation in all patients on an individual basis. Obstructive pathologies have to be corrected immediately and children with a positive family history should be followed carefully with respect to a high likelihood of stone re-growth and recurrence. Although specific management of each metabolic abnormality seems to be the key factor in the medical management of stone disease, as general advice each child should be forced to adequate fluid intake which will reveal the urine volume increase in accordance with the body mass index. Moreover, medical therapeutic agents which increase urine citrate levels should be encouraged.
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Affiliation(s)
- K Sarica
- Medical School, Pahinbey Medical Center, Department of Urology, University of Gaziantep, Gaziantep, Turkey.
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30
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Pelvicaliceal Anatomical Variation Between Stone Bearing and Normal Contralateral Kidneys???Does it Have an Impact on Stone Formation in Pediatric Patients With a Solitary Lower Caliceal Stone? J Urol 2006. [DOI: 10.1097/00005392-200601000-00097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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31
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Gurocak S, Kupeli B, Acar C, Guneri C, Tan MO, Bozkirli I. Pelvicaliceal Anatomical Variation Between Stone Bearing and Normal Contralateral Kidneys—Does it Have an Impact on Stone Formation in Pediatric Patients With a Solitary Lower Caliceal Stone? J Urol 2006; 175:270-5; discussion 275. [PMID: 16406924 DOI: 10.1016/s0022-5347(05)00010-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2005] [Indexed: 11/30/2022]
Abstract
PURPOSE We aimed to investigate the probable effect of pelvicaliceal anatomical differences between stone bearing and normal contralateral kidneys on the etiology of stone formation in children with a solitary lower pole caliceal stone. MATERIALS AND METHODS We reviewed the clinical records of 25 pediatric patients who underwent SWL for a solitary lower caliceal stone and 15 healthy pediatric patients who served as controls. Lower pole IPA, IL and IW, together with other caliceal variables obtained from the pelvicaliceal anatomy of the stone bearing and contralateral normal kidneys of patients with urolithiasis, and both kidneys of the control group were measured based on excretory urography. Also, total pelvicaliceal volume for both kidneys was calculated. RESULTS Mean LIPAs of stone bearing kidneys compared to the normal contralateral kidneys was more acute, equal and wider in 52%, 16% and 32% of the patients, respectively. Mean pelvicaliceal volumes of the stone forming and normal kidneys were 1,553.8 mm(3) (range 242 to 7,107) and 581.0 mm(3) (90 to 2,662), respectively, and there was statistical significance only in pelvicaliceal volumes between the stone bearing and contralateral normal kidneys (p <0.001). CONCLUSIONS Our results reveal that IPA, IL and IW of calices do not have an effect on stone formation in pediatric patients. However, large pelvicaliceal volume seems to be a significant risk factor for stone formation in the lower calix, probably because it creates abnormal urodynamic and morphological features, especially when accompanied by other metabolic abnormalities.
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Affiliation(s)
- Serhat Gurocak
- Department of Urology, Gazi University School of Medicine, Ankara, Turkey
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32
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Abstract
Childhood urolithiasis remains endemic in certain parts of the world, namely, Turkey and the Far East. The prevalence of nephrolithiasis in North American children varies widely among geographic regions and accounts for 1 per 1000 to 1 per 7600 pediatric hospital admissions. Stones occur in children of all ages. The clinical manifestations of stone disease are often more subtle in children when compared with the dramatic adult presentation. This article discusses the evaluation and medical management of pediatric stone disease.
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Affiliation(s)
- Sharon M Bartosh
- Department of Pediatrics, University of Wisconsin, University of Wisconsin Children's Hospital, 600 Highland Avenue, Madison, WI 53792, USA
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33
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Butani L, Kalia A. Idiopathic hypercalciuria in children--how valid are the existing diagnostic criteria? Pediatr Nephrol 2004; 19:577-82. [PMID: 15054648 DOI: 10.1007/s00467-004-1470-8] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2003] [Revised: 02/11/2004] [Accepted: 02/12/2004] [Indexed: 10/26/2022]
Abstract
Idiopathic hypercalciuria is a common metabolic abnormality in children of all ages. There is evidence of an association of idiopathic hypercalciuria with nephrolithiasis, hematuria, and osteoporosis. However, much of this evidence is anecdotal and the precise role of hypercalciuria in the pathogenesis of these conditions is far from clear. Furthermore, the precise definition of idiopathic hypercalciuria has not yet been established. The methodologies for quantitating urinary calcium excretion have also not been standardized, adding another potential confounding factor to the accurate interpretation of urinary calcium excretion. Long-term studies on the natural history of unselected children with idiopathic hypercalciuria are needed to establish the true clinical significance of this condition. The focus of this review is to critically evaluate the methods currently being used to measure urinary calcium excretion in children and to assess the validity of existing criteria for diagnosing idiopathic hypercalciuria.
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Affiliation(s)
- Lavjay Butani
- Section of Pediatric Nephrology, Department of Pediatrics, University of California Davis Medical Center, 2516 Stockton Boulevard, 3rd Floor, CA 95817, Sacramento, USA.
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34
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Escribano J, Balaguer A, Feliu A, Pagone F, Roqué IFM. Pharmacological interventions for preventing complications in idiopathic hypercalciuria. THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS 2004. [DOI: 10.1002/14651858.cd004754] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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35
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Coward RJM, Peters CJ, Duffy PG, Corry D, Kellett MJ, Choong S, van't Hoff WG. Epidemiology of paediatric renal stone disease in the UK. Arch Dis Child 2003; 88:962-5. [PMID: 14612355 PMCID: PMC1719348 DOI: 10.1136/adc.88.11.962] [Citation(s) in RCA: 129] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
BACKGROUND The previous epidemiological study of paediatric nephrolithiasis in Britain was conducted more than 30 years ago. AIMS To examine the presenting features, predisposing factors, and treatment strategies used in paediatric stones presenting to a British centre over the past five years. METHODS A total of 121 children presented with a urinary tract renal stone, to one adult and one paediatric centre, over a five year period (1997-2001). All children were reviewed in a dedicated stone clinic and had a full infective and metabolic stone investigative work up. Treatment was assessed by retrospective hospital note review. RESULTS A metabolic abnormality was found in 44% of children, 30% were classified as infective, and 26% idiopathic. Bilateral stones on presentation occurred in 26% of the metabolic group compared to 12% in the infective/idiopathic group (odds ratio 2.7, 95% CI 1.03 to 7.02). Coexisting urinary tract infection was common (49%) in the metabolic group. Surgically, minimally invasive techniques (lithotripsy, percutaneous nephrolithotomy, and endoscopy) were used in 68% of patients. CONCLUSIONS There has been a shift in the epidemiology of paediatric renal stone disease in the UK over the past 30 years. Underlying metabolic causes are now the most common but can be masked by coexisting urinary tract infection. Treatment has progressed, especially surgically, with sophisticated minimally invasive techniques now employed. All children with renal stones should have a metabolic screen.
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Affiliation(s)
- R J M Coward
- Nephro-Urology Unit, Institute of Child Health, London, UK.
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36
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Abstract
Urinary stones in children are usually genetic and most commonly due to hypercalciuria. Symptoms of urolithiasis in children differ among age groups. Isolated hematuria in children may be caused by hypercalciuria and precede calculus formation. Careful evaluation successfully identifies the cause of urinary stones in most children, although diagnostic criteria may vary in different age groups. Therapies should be targeted to the underlying diagnosis.
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Affiliation(s)
- F Bruder Stapleton
- Children's Hospital and Regional Medical Center, University of Washington Seattle, 4800 Sand Point Way North East, CH-65, Seattle, WA 98105, USA.
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37
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Botzenhart E, Vester U, Schmidt C, Hesse A, Halber M, Wagner C, Lang F, Hoyer P, Zerres K, Eggermann T. Cystinuria in children: distribution and frequencies of mutations in the SLC3A1 and SLC7A9 genes. Kidney Int 2002; 62:1136-42. [PMID: 12234283 DOI: 10.1111/j.1523-1755.2002.kid552.x] [Citation(s) in RCA: 54] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND Cystinuria is a common inherited disorder of defective renal reabsorption of cystine, ornithine, lysine and arginine leading to nephrolithiasis. Two responsible genes have been identified so far: Mutations in the SLC3A1 gene encoding the heavy chain rbAT of the renal cystine transport system rbAT/b(0,+)AT cause cystinuria type I, while variants in SLC7A9, the gene of its light chain b(0,+)AT, have been demonstrated in non-type I cystinuria. In this study, we searched for mutations in both genes in a cohort of children with cystinuria. METHODS Twenty-one cystinuric children from 16 families were analyzed by mutational analysis of the genes SLC3A1 and the SLC7A9. The patients were classified by the urinary amino acid excretion profile of their parents. Additionally, 10 unclassified patients were screened for genomic variants. The screening techniques included single strand conformation polymorphism analysis, restriction assays and direct sequencing. RESULTS Two novel mutations were identified in SLC3A1 and three in SLC7A9; three were missense mutations and two frameshift mutations. In the pediatric patients, mutations were found in 54% of type I (SLC3A1) and in 25% of non-type I (SLC7A9) chromosomes. For this group of patients a total detection rate of 46.6% for mutations in both genes was delineated. In the cohort of unclassified 10 patients, 70% of mutations were determined. M467T and G105R were the preponderant mutations in SLC3A1 and SLC7A9, respectively; T216M was the major mutation in Turkey and Greece. CONCLUSIONS The detection rate for mutations in SLC3A1 and SLC7A9 in children was 54% in the SLC3A1 gene for type I chromosomes and 25% in the SLC7A9 gene for non-type I chromosomes. It was lower than that in 10 further patients with an unclassified cystinuria, although the clinical characterization in the first group was more stringent; additionally, different spectrums of mutations were observed. The lack of detectable mutations in many patients indicates the possibility of other yet unidentified genes involved in cystinuria. We could not correlate the severity of the disease to the type of cystinuria in the pediatric patients.
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Affiliation(s)
- Elke Botzenhart
- Institute of Human Genetics, Technical University of Aachen, Pauwelsstrasse 30, D-52074 Aachen, Germany
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38
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Monico CG, Persson M, Ford GC, Rumsby G, Milliner DS. Potential mechanisms of marked hyperoxaluria not due to primary hyperoxaluria I or II. Kidney Int 2002; 62:392-400. [PMID: 12110000 DOI: 10.1046/j.1523-1755.2002.00468.x] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Hyperoxaluria may be idiopathic, secondary, or due to primary hyperoxaluria (PH). Hepatic alanine:glyoxylate aminotransferase (AGT) or glyoxylate/hydroxypyruvate reductase (GR/HPR) deficiency causes PHI or PHII, respectively. Hepatic glycolate oxidase (GO) is a candidate enzyme for a third form of inherited hyperoxaluria. METHODS Six children were identified with marked hyperoxaluria, urolithiasis, and normal hepatic AGT (N = 5) and GR/HPR (N = 4). HPR was below normal and GR not measured in one. Of an affected sibling pair, only one underwent biopsy. GO mutation screening was performed, and dietary oxalate (Diet(ox)), enteric oxalate absorption (EOA) measured using [13C2] oxalate, renal clearance (GFR), fractional oxalate excretion (FE(ox)) in the children, and urine oxalate in first-degree relatives (FDR) to understand the etiology of the hyperoxaluria. RESULTS Mean presenting age was 19.2 months and urine oxalate 1.3 +/- 0.5 mmol/1.73 m2/24 h (mean +/- SD). Two GO sequence changes (T754C, IVS3 - 49 C>G) were detected which were not linked to the hyperoxaluria. Diet(ox) was 42 +/- 31 mg/day. EOA was 9.4 +/- 3.6%, compared with 7.6 +/- 1.2% in age-matched controls (P = 0.33). GFR was 90 +/- 19 mL/min/1.73 m2 and FE(ox) 4.2 +/- 1.4. Aside from the two brothers, hyperoxaluria was not found in FDR. CONCLUSIONS These patients illustrate a novel form of hyperoxaluria and urolithiasis, without excess Diet(ox), enteric hyper-absorption, or hepatic AGT, GR/HPR deficiency. Alterations in pathways of oxalate synthesis, in liver or kidney, or in renal tubular oxalate handling are possible explanations. The affected sibling pair suggests an inherited basis.
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Affiliation(s)
- Carla G Monico
- Division of Nephrology, General Clinical Research Center, Mayo Clinic Rochester, Minnesota 55905, USA.
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Narendra A, White MP, Rolton HA, Alloub ZI, Wilkinson G, McColl JH, Beattie J. Nephrocalcinosis in preterm babies. Arch Dis Child Fetal Neonatal Ed 2001; 85:F207-13. [PMID: 11668166 PMCID: PMC1721318 DOI: 10.1136/fn.85.3.f207] [Citation(s) in RCA: 39] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
OBJECTIVES To determine prospectively the incidence and cause of nephrocalcinosis in preterm infants. STUDY DESIGN Inborn babies of gestation less than 32 weeks or birth weight less than 1500 g were eligible to be entered into a prospective observational study. Two renal ultrasound scans were performed, the first at 1 month postnatal age and the second at term or discharge. Data were collected on gestation, birth weight, sex, race, family history of renal calculi, oliguria on first day, respiratory support (ventilation, steroid, and oxygen dependency), and use of nephrotoxic drugs (gentamicin, vancomycin, and frusemide). Intake of fluid, calcium, and phosphate and plasma urea, creatinine, calcium, and phosphate were recorded for the first 6 weeks of life. Random urinary calcium/creatinine, oxalate/creatinine, and urate/creatinine ratios and tubular absorption of phosphate were measured once at term. RESULTS A total of 101 preterm infants were studied. Twenty three (23%) had abnormal ultrasound scans. Sixteen (16%) had nephrocalcinosis. On univariate analysis, gestational age, male sex, duration of ventilation, oxygen dependency, duration and frequency of gentamicin treatment, toxic gentamicin/vancomycin levels, and postnatal dexamethasone were significantly associated with nephrocalcinosis. In addition, babies with nephrocalcinosis had a lower intake of fluid, calcium, and phosphate, longer duration of total parenteral nutrition, and higher urinary oxalate/creatinine and urate/creatinine ratios than infants who did not have the condition. There was also a significant association with plasma urea and creatinine but not with plasma calcium or phosphate or urinary calcium. Multivariate analysis showed that the strongest predictors of nephrocalcinosis were duration of ventilation, toxic gentamicin/vancomycin levels, low fluid intake, and male sex. CONCLUSION 16% of babies born at less than 32 weeks gestation developed nephrocalcinosis. The multifactorial origin, in particular, the association with extreme prematurity and severity of respiratory disease, is confirmed. In addition, an association with male sex, frequency and duration of gentamicin use, and high urinary oxalate and urate excretion is shown.
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MESH Headings
- Aminoglycosides
- Anti-Bacterial Agents/adverse effects
- Confidence Intervals
- Female
- Glycopeptides
- Humans
- Incidence
- Infant
- Infant, Newborn
- Infant, Premature, Diseases/diagnostic imaging
- Infant, Premature, Diseases/epidemiology
- Infant, Premature, Diseases/etiology
- Infant, Very Low Birth Weight
- Logistic Models
- Male
- Nephrocalcinosis/diagnostic imaging
- Nephrocalcinosis/epidemiology
- Nephrocalcinosis/etiology
- Prospective Studies
- Respiration, Artificial/adverse effects
- Risk Factors
- Scotland/epidemiology
- Sex Factors
- Statistics, Nonparametric
- Time Factors
- Ultrasonography
- Water-Electrolyte Imbalance/complications
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Affiliation(s)
- A Narendra
- Department of Neonatology, The Qeen Mother's Hospital, Glasgow G3 8SJ, UK.
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40
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41
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Abstract
PURPOSE This study defines to what extent hypercalciuria represents a risk factor for recurrent calcium oxalate or nonstruvite stones. Long-term followup of children with hypercalciuria after an initial stone episode allowed us to determine the rate of stone recurrence. MATERIALS AND METHODS A total of 44 pediatric patients with stones were diagnosed with hypercalciuria, including 7 with structural abnormalities and 37 with normal anatomy. Of these patients 27 had adequate long-term followup. RESULTS There were 9 stone recurrences in the 27 patients who were evaluated long term for an overall recurrence rate of 33%. Recurrences developed 3 to 15 years after the initial episode (average time to recurrence 7.2 years), and none of the patients with structural abnormalities had hydronephrosis at recurrence. Of the 9 patients with stone recurrences 3 were female and 6 were male, and 4 had multiple stone recurrence episodes. Of these 9 cases of recurrent stones 8 had a positive family history for stone disease in a first degree relative, whereas only 8 of 18 cases without stone recurrence had a positive family history (p = 0. 04). CONCLUSIONS Hypercalciuria is a risk factor for recurrence in the pediatric patient with stones with and without structural abnormalities. New stones can occur several years after the initial episode and can extend through postpuberty.
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Affiliation(s)
- H N Noe
- Department of Urology, LeBonheur Children's Medical Center and University of Tennessee, Memphis, Memphis, Tennessee, USA
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42
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43
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Abstract
Urolithiasis in childhood is of diverse etiology requiring carefully planned individualized diagnostic and management protocols. The efficiency in diagnosis and management of urolithiasis in childhood follows a learning curve, especially when using the more recent technical innovations for management of urinary calculi. With current technical sophistication of transurethral and percutaneous techniques and ESWL, management of urolithiasis during childhood should be relatively straightforward as monotherapy using a single modality or as a combined approach with one or more techniques, saving open surgical intervention for situations where the new technology is either unavailable or inappropriate, or when surgical reconstruction of the urinary tract is necessary to forestall recurrent calculus formation. Postoperative morbidity after management of urinary calculi during childhood appears insignificant; calculus recurrence is uncommon. Long-term postoperative follow-up is mandatory, especially after using the newer technical innovations for urinary calculus management during childhood.
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Affiliation(s)
- R L Kroovand
- Department of Urology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina, USA
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44
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Affiliation(s)
- E N Pattishall
- Department of Cardiovascular/Critical Care Medicine, Glaxo Wellcome, Inc., Research Triangle Park, North Carolina, USA
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45
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Affiliation(s)
- T D Cohen
- Division of Urology, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
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46
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Abstract
The introduction of renal ultrasound technology has shown renal calcification to be more common in infancy than was previously believed. Understanding the role of inhibitors and promoters in crystal formation helps elucidate the pathophysiology of nephrocalcinosis. Identification of the presence or absence of hypercalcemia and hypercalciuria is an effective way to direct the diagnostic work-up of infants with nephrocalcinosis. The sonographic image of renal calcification resolves spontaneously in many infants. Whether microscopic nephrocalcinosis persists below the threshold of ultrasonographic detection is unknown. Renal calcification can be associated with persistent renal function abnormalities if hypercalciuria continues, such as in VLBW infants who receive long-term furosemide therapy after discharge from the hospital. Renal calcification may also progress to renal failure, such as in infants with primary hyperoxaluria, owing to the persistence of hyperoxaluria, a potent promoter of calcium crystal formation.
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Affiliation(s)
- M G Karlowicz
- Department of Pediatrics, Eastern Virginia Medical School, Norfolk, USA
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47
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Abstract
Urinary calcium excretion was measured in an unselected population of 153 healthy Swedish children aged 2-18 years. Urine was collected after an ordinary meal. Urinary calcium excretion was measured as the calcium/creatinine concentration ratio (UCa/Cr) and expressed in mmol/l per mmol/l. UCa/Cr was 0.44 +/- 0.379 (mean +/- SD). As the UCa/Cr in this childhood population was not distributed in a normal manner, the results are more correctly presented as the 50th (0.33) and 97th (1.5) centiles. There was a weak but significant correlation between UCa/Cr and age, with higher values in the lower age groups. There was no correlation between UCa/Cr and the anamnestic intake of cow's milk. Repeated samples from some children showed a coefficient of variation between days of 30-40%. The upper limits of normal UCa/Cr (97th centile = 1.5; +2 SD = 1.2) in this investigation were higher than what is considered normal by others. In spite of this, none of the children had a history of renal stone disease or any other symptoms of hypercalciuria. Renal stone disease is thought to be rare in Swedish children although the real incidence is not known. The diagnosis of hypercalciuria should be based on repeated samples from an individual with symptoms and related to age-related reference values from the same population group.
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Affiliation(s)
- E Esbjörner
- Department of Paediatrics, Orebro Medical Centre Hospital, Sweden
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48
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Vachvanichsanong P, Malagon M, Moore ES. Urinary incontinence due to idiopathic hypercalciuria in children. J Urol 1994; 152:1226-8. [PMID: 8072109 DOI: 10.1016/s0022-5347(17)32554-5] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Idiopathic hypercalciuria is known to cause many nonstone urinary tract disorders in childhood. In addition to being the most common cause of microhematuria in children, our study demonstrates that idiopathic hypercalciuria is also frequently associated with urinary incontinence of all types. Of 124 children evaluated for idiopathic hypercalciuria 28 (23%) had urinary incontinence. Of the 28 children 15 (54%) had nocturnal, 6 (21%) diurnal, and 7 (25%) nocturnal and diurnal incontinence. The random urinary calcium-creatinine ratio, which was used to screen for hypercalciuria, should be part of the initial evaluation for urinary incontinence in children. Diagnosis may be confirmed by quantitative urinary calcium excretion. Most urinary incontinence in children that is due to idiopathic hypercalciuria responds to a combination of general treatment for hypercalciuria or thiazide diuretics.
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Affiliation(s)
- P Vachvanichsanong
- Department of Pediatrics, University of Tennessee Graduate School of Medicine, Knoxville 37920
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49
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De Santo NG, Di Iorio B, Capasso G, Paduano C, Stamler R, Langman CB, Stamler J. Population based data on urinary excretion of calcium, magnesium, oxalate, phosphate and uric acid in children from Cimitile (southern Italy). Pediatr Nephrol 1992; 6:149-57. [PMID: 1571211 DOI: 10.1007/bf00866297] [Citation(s) in RCA: 51] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Population based data on 24-h urinary excretion of calcium, oxalate, magnesium, phosphate, uric acid and creatinine were collected from 220 children (aged 3-16 years) living in Cimitile, Campania, southern Italy. Mean excretion rates for 7 days were correlated with age, body weight, body mass index and height. The prevalence of hypercalciuria (greater than 4 mg/kg body weight) and of hyperoxaluria (greater than 60 mg/day) were 9.1% and 1.8%, respectively. The same 20 children were also identified as hypercalciuric when a calcium/creatinine ratio of greater than 0.15 was considered. No significant differences between boys and girls were found in the urinary excretion of the five constituents implicated in urolithiasis. The study data provide additional childhood reference values for urinary excretion of compounds related to stone formation.
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Affiliation(s)
- N G De Santo
- Department of Paediatric Nephrology, 1st Faculty of Medicine, University Federico II, Naples, Italy
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50
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Perrone HC, dos Santos DR, Santos MV, Pinheiro ME, Toporovski J, Ramos OL, Schor N. Urolithiasis in childhood: metabolic evaluation. Pediatr Nephrol 1992; 6:54-6. [PMID: 1536741 DOI: 10.1007/bf00856834] [Citation(s) in RCA: 57] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
In order to determine metabolic disorders in children with urolithiasis, 50 patients with urinary calculi were studied. Abdominal pain and/or haematuria were the most predominant symptoms. Surgical procedures were required in 22% of these children and urinary tract infection was observed in 34% of this group. Only 2 children had anatomical malformations of the urinary tract. Absorptive hypercalciuria (32%), renal hypercalciuria (34%) and uric acid hyperexcretion (24%) were the most common metabolic abnormalities in these children. We were unable to find an underlying metabolic abnormality in only 14% of the patients. These data suggest that appropriate metabolic study will allow rational management of children with urinary stones.
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Affiliation(s)
- H C Perrone
- Department of Medicine, Escola Paulista of Medicina, São Paulo, Brazil
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