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Gabai P, Novel-Catin E, Reynaud Q, Nove-Josserand R, Pelletier S, Fouque D, Koppe L, Durieu I. Kidney effects of triple CFTR modulator therapy in people with cystic fibrosis. Clin Kidney J 2024; 17:sfae256. [PMID: 39359568 PMCID: PMC11443170 DOI: 10.1093/ckj/sfae256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Indexed: 10/04/2024] Open
Abstract
Background Elexacaftor/tezacaftor/ivacaftor (ETI) is a new cystic fibrosis transmembrane conductance regulator (CFTR) modulator that has transformed the respiratory prognosis of people with cystic fibrosis (pwCF). However, its impact on other organs such as the kidneys, where CFTR is expressed, remains unclear. Since pwCF are risk of both kidney disease and urolithiasis, we aimed to study the potential effects of ETI on renal function, volume status, and risk factors for urolithiasis. Methods This prospective, observational, single-center, before-after cohort study, involved adult pwCF eligible for ETI. The changes in plasma and urinary profiles were assessed by comparing renal function (using 2021 CKD-EPIcreatinine and 2021 CKD-EPIcreatinine-cystatin C formulas), volume status (using aldosterone/renin ratio and blood pressure), and risk factors for urolithiasis, at the time of ETI introduction (M0) and 7 months after (M7). Results Nineteen pwCF were included. No significant change in renal function was observed between M0 and M7 (2021 CKD-EPIcreatinine: 105.5 ml/min/1.73 m² at M0 vs. 103.3 ml/min/1.73 m² at M7; P = .17). There was a significant reduction in aldosterone level (370.3 pmol/l at M0 vs. 232.4 pmol/l at M7; P = .02) and aldosterone/renin ratio (33.6 at M0 vs. 21.8 at M7; P = .03). Among the risk factors for urolithiasis, a significant reduction in magnesuria level was found (4.6 mmol/d at M0 vs. 3.8 mmol/d at M7; P = .01). Conclusion These findings suggest that ETI seem to have no short-term impact on the renal function of adult pwCF and appears to correct secondary hyperaldosteronism due to excessive sweat losses. Further investigations are needed to determine the potential impact of decreased magnesuria observed under ETI therapy on the risk of urolithiasis.
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Affiliation(s)
- Pierre Gabai
- Service de Néphrologie, Hospices Civils de Lyon, Hôpital Lyon Sud, 165 Chemin du Grand Revoyet, Pierre-Bénite, Rhône, France
| | - Etienne Novel-Catin
- Service de Néphrologie, Hospices Civils de Lyon, Hôpital Lyon Sud, 165 Chemin du Grand Revoyet, Pierre-Bénite, Rhône, France
| | - Quitterie Reynaud
- Centre de Ressource et de Compétences de la mucoviscidose, Service de médecine Interne et de Pathologie Vasculaire, Hospices Civils de Lyon, Hôpital Lyon Sud, 165 Chemin du Grand Revoyet, Pierre-Bénite, Rhône, France
- ERN-Lung Cystic Fibrosis Network, Frankfurt, Frankfurt Region, Germany
- RESearch on HealthcAre PErformance (RESHAPE), INSERM U1290, Claude Bernard Lyon 1 University, 8 Avenue Rockfeller, Lyon Cedex 08, Rhône, France
| | - Raphaële Nove-Josserand
- Centre de Ressource et de Compétences de la mucoviscidose, Service de médecine Interne et de Pathologie Vasculaire, Hospices Civils de Lyon, Hôpital Lyon Sud, 165 Chemin du Grand Revoyet, Pierre-Bénite, Rhône, France
| | - Solenne Pelletier
- Service de Néphrologie, Hospices Civils de Lyon, Hôpital Lyon Sud, 165 Chemin du Grand Revoyet, Pierre-Bénite, Rhône, France
| | - Denis Fouque
- Service de Néphrologie, Hospices Civils de Lyon, Hôpital Lyon Sud, 165 Chemin du Grand Revoyet, Pierre-Bénite, Rhône, France
- CarMeN Laboratory, INSERM, INRAE, Claude Bernard Lyon 1 University, Pierre-Bénite, Rhône, France
| | - Laetitia Koppe
- Service de Néphrologie, Hospices Civils de Lyon, Hôpital Lyon Sud, 165 Chemin du Grand Revoyet, Pierre-Bénite, Rhône, France
- CarMeN Laboratory, INSERM, INRAE, Claude Bernard Lyon 1 University, Pierre-Bénite, Rhône, France
| | - Isabelle Durieu
- Centre de Ressource et de Compétences de la mucoviscidose, Service de médecine Interne et de Pathologie Vasculaire, Hospices Civils de Lyon, Hôpital Lyon Sud, 165 Chemin du Grand Revoyet, Pierre-Bénite, Rhône, France
- ERN-Lung Cystic Fibrosis Network, Frankfurt, Frankfurt Region, Germany
- RESearch on HealthcAre PErformance (RESHAPE), INSERM U1290, Claude Bernard Lyon 1 University, 8 Avenue Rockfeller, Lyon Cedex 08, Rhône, France
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Taroni F, Peruzzi L, Longo G, Becherucci F, Malgieri G, D'Alessandro MM, Montini G. Lumasiran treatment in pediatric patients with PH1: real-world data within a compassionate use program in Italy. Clin Kidney J 2024; 17:sfae090. [PMID: 38742209 PMCID: PMC11089410 DOI: 10.1093/ckj/sfae090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Indexed: 05/16/2024] Open
Abstract
Background Primary hyperoxaluria (PH) is a rare, severe genetic disorder, characterized by increased urinary excretion of calcium oxalate, which is responsible for kidney damage and systemic clinical manifestations. Since the year 2020, a new molecule, lumasiran, based on RNA interference (RNAi) technology, has been added to the traditional therapeutic approach. The aim of this analysis was to define the baseline characteristics of a PH1 pediatric population treated with lumasiran in a compassionate-use program setting, and to evaluate the medium-term efficacy of this drug in the routine clinical setting. Methods A retrospective observational analysis was conducted in nine pediatric patients (male:female 5:4; median age at lumasiran start 1.9 years, range 0-14.1). Data concerning oxalate concentration in plasma and urine, kidney stones events, ultrasound and kidney function were collected during the study period (follow-up, mean ± standard deviation: 15.3 ± 5 months). Results In this analysis, a reduction in the urinary oxalate to creatinine ratio (reduction range within the sixth month of treatment from 25.8% to 69.6%, median 51.2%) as well as plasma oxalate concentration under the limit of supersaturation of oxalate in all the patients. Only one patient presented new stone events; kidney ultrasonographic findings related to nephrocalcinosis remained stable in eight out of nine patients. Glomerular filtration rate remained stable during treatment. No adverse events related to lumasiran were noted. Conclusion Data from this analysis support the efficacy and safety of lumasiran in a pediatric clinical setting, especially if administrated in early life.
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Affiliation(s)
- Francesca Taroni
- Pediatric Nephrology Dialysis and Transplant Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Licia Peruzzi
- Pediatric Nephrology Dialysis and Transplant Unit, Regina Margherita Children's Hospital, Torino, Italy
| | - Germana Longo
- Pediatric Nephrology, Dialysis and Transplant Unit, Department of Woman and Child Health, Azienda Ospedaliera-University of Padova, Padova, Italy
| | | | - Gabriele Malgieri
- Paediatric Nephrology, Dialysis and Renal Transplantation Santobono Pausilipon Children's Hospital, Naples, Italy
| | - Maria Michela D'Alessandro
- Pediatric Nephrology Unit, Azienda di Rilievo Nazionale ed Alta Specializzazione (ARNAS) Civico, Di Cristina, Benfratelli, Palermo, Italy
| | - Giovanni Montini
- Pediatric Nephrology Dialysis and Transplant Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Clinical Sciences and Community Health, University of Milano, Milan, Italy
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Taroni F, Berrettini A, Gnech M, Rella F, Manzoni GA, Montini G. Case Report: effect of lumasiran treatment in a late preterm baby with antenatal diagnosis of primary hyperoxaluria type 1. Front Pediatr 2024; 11:1338909. [PMID: 38293660 PMCID: PMC10825030 DOI: 10.3389/fped.2023.1338909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 12/22/2023] [Indexed: 02/01/2024] Open
Abstract
Background Primary hyperoxaluria type 1 (PH1) is a rare disease with autosomal recessive transmission, characterized by increased urinary excretion of oxalate, resulting in chronic kidney disease secondary to recurrent urolithiasis, nephrocalcinosis, and accumulation of oxalate in various organs and tissues (systemic oxalosis). Since 2020, an innovative pharmacological approach, namely, lumasiran, has been added to the therapeutic armamentarium (dialysis and liver-kidney transplantation). The purpose of this paper is to describe the effect of lumasiran initiated at 10 days of life in a newborn with prenatally diagnosed PH1. A female fetus was prenatally diagnosed with hyperoxaluria type 1, based on family history and genetic testing. Her brother had the onset of the disease at 2 months of age and underwent liver and kidney transplantation at 13 months and 8 years of age, respectively. The baby was born late preterm at 36 weeks + 4 days of gestation via spontaneous labor, and lumasiran for compassionate use was started on the tenth day of life. At 20 months of age, the baby showed normal urinary oxalate values and kidney function, while the plasma oxalate level was under the threshold of oversaturation. There were no signs of systemic oxalosis. Conclusions Early use of lumasiran in young infants, who do not yet show signs of the disease, represents a therapeutic challenge for the pediatric nephrologist. The ability of the drug to act on the hepatocyte of the newborn and the most appropriate dosage to be used in these very young babies have yet to be clarified.
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Affiliation(s)
- Francesca Taroni
- Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, Milano, Italy
| | - Alfredo Berrettini
- Department of Pediatric Urology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Michele Gnech
- Department of Pediatric Urology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Francesca Rella
- Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, Milano, Italy
| | - Gian Antonio Manzoni
- Department of Pediatric Urology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Giovanni Montini
- Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, Milano, Italy
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
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Hydration and Nephrolithiasis in Pediatric Populations: Specificities and Current Recommendations. Nutrients 2023; 15:nu15030728. [PMID: 36771434 PMCID: PMC9920266 DOI: 10.3390/nu15030728] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 01/19/2023] [Accepted: 01/27/2023] [Indexed: 02/05/2023] Open
Abstract
Renal lithiasis is less frequent in children than in adults; in pediatrics, lithiasis may be caused by genetic abnormalities, infections, and complex uropathies, but the association of urological and metabolic abnormalities is not uncommon. The aim of this study is to provide a synthesis of nephrolithiasis in children and to emphasize the role of hydration in its treatment. As an etiology is reported in 50% of cases, with a genetic origin in 10 to 20%, it is proposed to systematically perform a complete metabolic assessment after the first stone in a child. Recent data in the field reported increased incidence of pediatric urolithiasis notably for calcium oxalate stones. These changes in the epidemiology of stone components may be attributable to metabolic and environmental factors, where hydration seems to play a crucial role. In case of pediatric urolithiasis, whatever its cause, it is of utmost importance to increase water intake around 2 to 3 L/m2 per day on average. The objective is to obtain a urine density less than 1010 on a dipstick or below 300 mOsm/L, especially with the first morning urine. Some genetic diseases may even require a more active 24 h over-hydration, e.g., primary hyperoxaluria and cystinuria; in such cases naso-gastric tubes or G-tubes may be proposed. Tap water is adapted for children with urolithiasis, with limited ecological impact and low economical cost. For children with low calcium intake, the use of calcium-rich mineral waters may be discussed in some peculiar cases, even in case of urolithiasis. In contrast, sugar-sweetened beverages are not recommended. In conclusion, even if parents and patients sometimes have the feeling that physicians do not propose "fancy" therapeutic drugs, hydration and nutrition remain cornerstones of the management of pediatric urolithiasis.
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Understanding Cystic Fibrosis Comorbidities and Their Impact on Nutritional Management. Nutrients 2022; 14:nu14051028. [PMID: 35268004 PMCID: PMC8912424 DOI: 10.3390/nu14051028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 02/23/2022] [Accepted: 02/25/2022] [Indexed: 11/17/2022] Open
Abstract
Cystic fibrosis (CF) is a chronic, multisystem disease with multiple comorbidities that can significantly affect nutrition and quality of life. Maintaining nutritional adequacy can be challenging in people with cystic fibrosis and has been directly associated with suboptimal clinical outcomes. Comorbidities of CF can result in significantly decreased nutritional intake and intestinal absorption, as well as increased metabolic demands. It is crucial to utilize a multidisciplinary team with expertise in CF to optimize growth and nutrition, where patients with CF and their loved ones are placed in the center of the care model. Additionally, with the advent of highly effective modulators (HEMs), CF providers have begun to identify previously unrecognized nutritional issues, such as obesity. Here, we will review and summarize commonly encountered comorbidities and their nutritional impact on this unique population.
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Moryousef J, Kwong J, Kishibe T, Ordon M. Systematic Review of the Prevalence of Kidney Stones in Cystic Fibrosis. J Endourol 2021; 35:1693-1700. [PMID: 33906435 DOI: 10.1089/end.2021.0151] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Purpose: To investigate the prevalence of urolithiasis in cystic fibrosis (CF) and to summarize the available clinical features within this unique population. Methods: Studies reporting the prevalence of urolithiasis in CF patients were identified by a systematic search of the literature from inception to July 31, 2020 on three databases: Ovid Medline, Ovid Embase, and Web of Science. Data were extracted on a predetermined standardized form by two independent authors. Results: A total of 596 publications were retrieved and screened, 15 of which met the eligibility criteria. The publications were published between 1993 and 2019 and were all observational in design. There was a total of 2982 patients with CF included in this review. The overall prevalence of stone formation in the CF population was 4.6% (137/2982). The mean age of diagnosis was 25.1 ± 9.6 and ranged from 0.25 to 47. Ultrasound was the most common imaging modality for kidney stone diagnosis. There was no apparent sex difference, with a female to male ratio of 1:1. Surgical intervention was required in 37.8% (34/90) of cases. Stone recurrence was reported in 42.9% (33/77) of stone formers. Conclusions: This review provides the most recent update for the prevalence of urolithiasis in CF patients and summarizes the available clinical data. Our findings suggest that patients with CF could be at risk for developing stones at a younger age and require interventional management strategies at higher rates compared with the general population. Given the heterogeneity of the literature for urolithiasis in CF, larger population-based studies reporting the epidemiology, clinical features, and management strategies are required to further our understanding of urolithiasis in CF.
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Affiliation(s)
| | - Justin Kwong
- Division of Urology, Department of Surgery, St. Michael's Hospital, University of Toronto, Toronto, Canada
| | - Teruko Kishibe
- Health Sciences Library, St. Michael's Hospital, Unity Health Toronto, Toronto, Canada
| | - Michael Ordon
- Division of Urology, Department of Surgery, St. Michael's Hospital, University of Toronto, Toronto, Canada
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Wright JF, Craig WY, Lucas FL, Goldfarb DS, Zuckerman JB, Taylor EN. Urinary stone disease prevalence and associations in cystic fibrosis. Urolithiasis 2021; 49:415-423. [PMID: 33547925 DOI: 10.1007/s00240-021-01244-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Accepted: 01/13/2021] [Indexed: 11/25/2022]
Abstract
Cystic fibrosis (CF) may predispose patients to urinary stone disease (USD), but reported prevalence of USD in patients with CF in previous small studies is variable. To date, analysis of risk factors for USD within the CF population has been limited. We studied 29,396 patients in the Cystic Fibrosis Foundation Patient Registry to calculate age and sex-stratified prevalence of USD. For adult patients, we examined age and multivariable-adjusted cross-sectional associations between demographic and clinical factors, CFTR mutation class, and prevalent USD. Prevalence of USD was 0.4% (95% CI 0.3-0.5%) under age 18 years, 3.1% (2.7-3.6%) at 18-24 years, 6.4% (5.8-7.1%) at 25-34 years, 7.5% (6.5-8.5%) at 35-44 years, and 6.7% (5.8-7.8%) at 45 years and older. Prevalence for women was higher than men at younger (< 45 years) but not older ages (P value for interaction < 0.0005). Multivariable odds of prevalent USD were significantly increased for severe CFTR mutations, OR 1.53 (1.14-2.06), diabetes, OR 1.24 (1.03-1.50), hypertension, OR 1.58 (1.29-1.93), and chronic macrolide therapy, OR 1.27 (1.07-1.52). BMI was not associated with USD. USD prevalence in CF is similar to that in the general population. With the exception of BMI, known risk factors for USD in the general population also appear to be important for patients with CF. We identified several novel associations in CF patients, including greater prevalence of USD in individuals with severe CFTR mutations and among young women.
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Affiliation(s)
- Jeremy F Wright
- Division of Nephrology and Transplantation, Maine Medical Center, Tufts University School of Medicine, c/o Karen Kinne, 22 Bramhall Street, Portland, ME, 04102, USA.
| | - Wendy Y Craig
- Center for Outcomes Research and Evaluation, Maine Medical Center Research Institute, Tufts University School of Medicine, 509 Forest Avenue Suite 200, Portland, ME, 04102, USA
| | - F L Lucas
- Center for Outcomes Research and Evaluation, Maine Medical Center Research Institute, Tufts University School of Medicine, 509 Forest Avenue Suite 200, Portland, ME, 04102, USA
| | - David S Goldfarb
- Division of Nephrology, New York University School of Medicine, 150 East 32nd Street, 2nd Floor, New York, NY, 10016, USA
| | - Jonathan B Zuckerman
- Division of Pulmonary and Critical Care, Maine Medical Center, Tufts University School of Medicine, 22 Bramhall Street, Portland, ME, 04102, USA
| | - Eric N Taylor
- Division of Nephrology and Transplantation, Maine Medical Center, Tufts University School of Medicine, c/o Karen Kinne, 22 Bramhall Street, Portland, ME, 04102, USA.,FASN Section of Nephrology, VA Maine Healthcare System, 1 VA Center, Augusta, ME, 04330, USA
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Daudon M, Frochot V, Bazin D, Jungers P. Drug-Induced Kidney Stones and Crystalline Nephropathy: Pathophysiology, Prevention and Treatment. Drugs 2018; 78:163-201. [PMID: 29264783 DOI: 10.1007/s40265-017-0853-7] [Citation(s) in RCA: 90] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Drug-induced calculi represent 1-2% of all renal calculi. The drugs reported to produce calculi may be divided into two groups. The first one includes poorly soluble drugs with high urine excretion that favour crystallisation in the urine. Among them, drugs used for the treatment of patients with human immunodeficiency, namely atazanavir and other protease inhibitors, and sulphadiazine used for the treatment of cerebral toxoplasmosis, are the most frequent causes. Besides these drugs, about 20 other molecules may induce nephrolithiasis, such as ceftriaxone or ephedrine-containing preparations in subjects receiving high doses or long-term treatment. Calculi analysis by physical methods including infrared spectroscopy or X-ray diffraction is needed to demonstrate the presence of the drug or its metabolites within the calculi. Some drugs may also provoke heavy intra-tubular crystal precipitation causing acute renal failure. Here, the identification of crystalluria or crystals within the kidney tissue in the case of renal biopsy is of major diagnostic value. The second group includes drugs that provoke the formation of urinary calculi as a consequence of their metabolic effects on urinary pH and/or the excretion of calcium, phosphate, oxalate, citrate, uric acid or other purines. Among such metabolically induced calculi are those formed in patients taking uncontrolled calcium/vitamin D supplements, or being treated with carbonic anhydrase inhibitors such as acetazolamide or topiramate. Here, diagnosis relies on a careful clinical inquiry to differentiate between common calculi and metabolically induced calculi, of which the incidence is probably underestimated. Specific patient-dependent risk factors also exist in relation to urine pH, volume of diuresis and other factors, thus providing a basis for preventive or curative measures against stone formation.
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Affiliation(s)
- Michel Daudon
- CRISTAL Laboratory, Tenon Hospital, Paris, France.
- Laboratoire des Lithiases, Service des Explorations Fonctionnelles Multidisciplinaires, AP-HP, Hôpital Tenon, 4, rue de la Chine, 75020, Paris, France.
- INSERM, UMRS 1155 UPMC, Tenon Hospital, Paris, France.
| | - Vincent Frochot
- Laboratoire des Lithiases, Service des Explorations Fonctionnelles Multidisciplinaires, AP-HP, Hôpital Tenon, 4, rue de la Chine, 75020, Paris, France
- INSERM, UMRS 1155 UPMC, Tenon Hospital, Paris, France
| | - Dominique Bazin
- CNRS, UPMC, Paris, France
- Laboratoire de Chimie de la Matière Condensée de Paris, UPMC, Paris, France
| | - Paul Jungers
- Department of Nephrology, Necker Hospital, AP-HP, Paris, France
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Peck AB, Canales BK, Nguyen CQ. Oxalate-degrading microorganisms or oxalate-degrading enzymes: which is the future therapy for enzymatic dissolution of calcium-oxalate uroliths in recurrent stone disease? Urolithiasis 2015; 44:45-50. [PMID: 26645869 DOI: 10.1007/s00240-015-0845-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Accepted: 11/05/2015] [Indexed: 12/25/2022]
Abstract
Renal urolithiasis is a pathological condition common to a multitude of genetic, physiological and nutritional disorders, ranging from general hyperoxaluria to obesity. The concept of quickly dissolving renal uroliths via chemolysis, especially calcium-oxalate kidney stones, has long been a clinical goal, but yet to be achieved. Over the past 25 years, there has been a serious effort to examine the prospects of using plant and microbial oxalate-degrading enzymes known to catabolize oxalic acid and oxalate salts. While evidence is emerging that bacterial probiotics can reduce recurrent calcium-oxalate kidney stone disease by lowering systemic hyperoxaluria, the possible use of free oxalate-degrading enzyme therapy remains a challenge with several hurdles to overcome before reaching clinical practice.
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Affiliation(s)
- Ammon B Peck
- Department of Infectious Diseases and Pathology, University of Florida College of Veterinary Medicine, P.O Box 100125, VAB, Bldg 1017, Gainesville, FL, 32610, USA.
| | - Benjamin K Canales
- Department of Urology, University of Florida College of Medicine, P.O. Box 100247, 1600 SW Archer Rd, Gainesville, FL, 32610, USA
| | - Cuong Q Nguyen
- Department of Infectious Diseases and Pathology, University of Florida College of Veterinary Medicine, P.O Box 100125, VAB, Bldg 1017, Gainesville, FL, 32610, USA
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Reichman G, De Boe V, Braeckman J, Michielsen D. Urinary incontinence in patients with cystic fibrosis. Scand J Urol 2015; 50:128-31. [DOI: 10.3109/21681805.2015.1096826] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Bhasin B, Ürekli HM, Atta MG. Primary and secondary hyperoxaluria: Understanding the enigma. World J Nephrol 2015; 4:235-244. [PMID: 25949937 PMCID: PMC4419133 DOI: 10.5527/wjn.v4.i2.235] [Citation(s) in RCA: 104] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2014] [Revised: 08/29/2014] [Accepted: 02/09/2015] [Indexed: 02/05/2023] Open
Abstract
Hyperoxaluria is characterized by an increased urinary excretion of oxalate. Primary and secondary hyperoxaluria are two distinct clinical expressions of hyperoxaluria. Primary hyperoxaluria is an inherited error of metabolism due to defective enzyme activity. In contrast, secondary hyperoxaluria is caused by increased dietary ingestion of oxalate, precursors of oxalate or alteration in intestinal microflora. The disease spectrum extends from recurrent kidney stones, nephrocalcinosis and urinary tract infections to chronic kidney disease and end stage renal disease. When calcium oxalate burden exceeds the renal excretory ability, calcium oxalate starts to deposit in various organ systems in a process called systemic oxalosis. Increased urinary oxalate levels help to make the diagnosis while plasma oxalate levels are likely to be more accurate when patients develop chronic kidney disease. Definitive diagnosis of primary hyperoxaluria is achieved by genetic studies and if genetic studies prove inconclusive, liver biopsy is undertaken to establish diagnosis. Diagnostic clues pointing towards secondary hyperoxaluria are a supportive dietary history and tests to detect increased intestinal absorption of oxalate. Conservative treatment for both types of hyperoxaluria includes vigorous hydration and crystallization inhibitors to decrease calcium oxalate precipitation. Pyridoxine is also found to be helpful in approximately 30% patients with primary hyperoxaluria type 1. Liver-kidney and isolated kidney transplantation are the treatment of choice in primary hyperoxaluria type 1 and type 2 respectively. Data is scarce on role of transplantation in primary hyperoxaluria type 3 where there are no reports of end stage renal disease so far. There are ongoing investigations into newer modalities of diagnosis and treatment of hyperoxaluria. Clinical differentiation between primary and secondary hyperoxaluria and further between the types of primary hyperoxaluria is very important because of implications in treatment and diagnosis. Hyperoxaluria continues to be a challenging disease and a high index of clinical suspicion is often the first step on the path to accurate diagnosis and management.
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12
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Renal diseases in adults with cystic fibrosis: a 40 year single centre experience. J Nephrol 2015; 28:585-91. [PMID: 25712235 DOI: 10.1007/s40620-015-0179-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2014] [Accepted: 02/05/2015] [Indexed: 10/23/2022]
Abstract
BACKGROUND There is a sizable literature describing renal disease in patients with cystic fibrosis. Previous studies have focused on single disease processes alone, most commonly renal stone disease or acute kidney injury. In this study we report for the first time on the prevalence of all forms of renal disease in a cystic fibrosis population. METHODS A retrospective review of adult patients with cystic fibrosis attending the Adult Cystic Fibrosis Department at the Royal Brompton Hospital was carried out by searching the department's database to identify patients with renal problems and subsequently retrieving clinical information from medical notes. RESULTS The prevalence of all renal diseases in our population was 5.1 %. The most commonly identified problem was renal stones. At 2.0 % the prevalence of renal stones in adult patients with cystic fibrosis was comparable to the general population. A range of other renal diseases were identified, the next most common being drug-induced acute kidney injury. CONCLUSIONS A range of cystic fibrosis independent and attributable diseases has been identified but no cystic fibrosis specific disease. In contrast to other cystic fibrosis centres no increased prevalence of renal stones was found.
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13
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A review of renal disease in cystic fibrosis. J Cyst Fibros 2013; 12:309-17. [DOI: 10.1016/j.jcf.2013.03.005] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2012] [Revised: 03/13/2013] [Accepted: 03/14/2013] [Indexed: 01/10/2023]
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Cochat P, Hulton SA, Acquaviva C, Danpure CJ, Daudon M, De Marchi M, Fargue S, Groothoff J, Harambat J, Hoppe B, Jamieson NV, Kemper MJ, Mandrile G, Marangella M, Picca S, Rumsby G, Salido E, Straub M, van Woerden CS. Primary hyperoxaluria Type 1: indications for screening and guidance for diagnosis and treatment. Nephrol Dial Transplant 2012; 27:1729-36. [PMID: 22547750 DOI: 10.1093/ndt/gfs078] [Citation(s) in RCA: 217] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Primary hyperoxaluria Type 1 is a rare autosomal recessive inborn error of glyoxylate metabolism, caused by a deficiency of the liver-specific enzyme alanine:glyoxylate aminotransferase. The disorder results in overproduction and excessive urinary excretion of oxalate, causing recurrent urolithiasis and nephrocalcinosis. As glomerular filtration rate declines due to progressive renal involvement, oxalate accumulates leading to systemic oxalosis. The diagnosis is based on clinical and sonographic findings, urine oxalate assessment, enzymology and/or DNA analysis. Early initiation of conservative treatment (high fluid intake, pyridoxine, inhibitors of calcium oxalate crystallization) aims at maintaining renal function. In chronic kidney disease Stages 4 and 5, the best outcomes to date were achieved with combined liver-kidney transplantation.
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Affiliation(s)
- Pierre Cochat
- Reference Center for Rare Renal Diseases & EPICIME, Department of Paediatrics, Hospices Civils de Lyon and Université Claude-Bernard Lyon 1, Lyon, France.
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Andrieux A, Harambat J, Bui S, Nacka F, Iron A, Llanas B, Fayon M. Renal impairment in children with cystic fibrosis. J Cyst Fibros 2010; 9:263-8. [PMID: 20413352 DOI: 10.1016/j.jcf.2010.03.006] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2009] [Revised: 03/06/2010] [Accepted: 03/11/2010] [Indexed: 11/25/2022]
Abstract
BACKGROUND Due to the improvement in life expectancy in cystic fibrosis (CF), co-morbidities such as renal function impairment may be more frequent. AIM To determine the prevalence of renal disease in children with CF and to identify associated risk factors. METHODS A single-center retrospective study analyzing the genetic, clinical and therapeutic characteristics of 112 children. The estimated glomerular filtration rate (GFR), microalbuminuria and lithiasic risk factors were assessed. RESULTS The median calculated GFR (Schwartz) was 123, 161 and 155ml/min/1.73m(2) in children aged 1, 6 and 15years, respectively. The cumulative dose of aminoglycosides was not correlated to GFR. Microalbuminuria was present in 22/38 patients. Hyperoxaluria was observed in 58/83 patients and was associated with a severe genotype, pancreas insufficiency and liver disease. Hypercalciuria, hyperuricuria and hypocitraturia were identified in 16/87, 15/83 and 57/76 patients, respectively. CONCLUSION Renal impairment in CF has various presentations. There appears to be low levels of renal impairment in children with CF. However, the risk of oxalocalcic urolithiasis is enhanced, and GFR may be underestimated by the Schwartz formula. Further studies using measured GFR techniques are thus warranted.
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Affiliation(s)
- Annick Andrieux
- CHU de Bordeaux, Centre de Ressources et de Compétences de la Mucoviscidose pédiatrique, Hôpital Pellegrin Enfants, Bordeaux, France
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[Renal diseases in cystic fibrosis]. Nephrol Ther 2009; 5:550-8. [PMID: 19589743 DOI: 10.1016/j.nephro.2009.05.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2009] [Revised: 05/11/2009] [Accepted: 05/11/2009] [Indexed: 11/23/2022]
Abstract
Patients with cystic fibrosis (CF) show a continuing improvement in their life expectancy thanks to advances in knowledge of this disorder, allowing better multidisciplinary routine monitoring and earlier therapeutic interventions. Likewise, more than of 40% of these patients are adults and CF is no more only a pediatric disease. Due to their higher life expectancy, CF patients present new and unusual complications that were not recorded before. Among them, some renal disorders have to be added to the CF-related renal diseases. They are due to frequent and prolonged exposure to various potentially nephrotoxic factors that need to be taken into account early enough in order to avoid renal failure : essentially risk factors for kidney stones formation, bacterial infections with their associated immune complexes diseases, nephrotoxic effects of antibiotics, diabetes mellitus. Because we observed a case of IgA glomerulonephritis in a 35-year-old patient with cystic fibrosis, we have searched about all these renal consequences due to this affection and here report them.
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Traxer O, Lechevallier E, Saussine C. [Urolithiasis in childhood]. Prog Urol 2008; 18:1005-14. [PMID: 19033072 DOI: 10.1016/j.purol.2008.09.037] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2008] [Accepted: 09/02/2008] [Indexed: 11/25/2022]
Affiliation(s)
- O Traxer
- Service d'urologie, hôpital Tenon, 4, rue de La-Chine, 75970 Paris cedex 20, France.
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Al-Shawwa BA, Rao AR. Cystic fibrosis and renal disease: a case report. J Med Case Rep 2007; 1:24. [PMID: 17547751 PMCID: PMC1896172 DOI: 10.1186/1752-1947-1-24] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2007] [Accepted: 06/04/2007] [Indexed: 11/10/2022] Open
Abstract
Background Cystic fibrosis (CF) is an autosomal recessive disease that is predominantly seen in the Caucasian population and involves multiple organs. Traditionally it has been thought that the kidney is the only organ which does not seem to be generally affected by the disease although the cystic fibrosis transmembrane conductance regulator (CFTR) gene is expressed in the kidney. Case presentation We report the case of an 11 year old boy with cystic fibrosis and nephrotic syndrome and review the literature that describes nephrotic syndrome and renal involvement in cystic fibrosis. Conclusion With continued advances in the management of cystic fibrosis and improvement in life expectancy, several unrecognized co-morbidities are expected to emerge. It is important to screen patients for possible co-morbidities. Urine analysis may be helpful in this group of patients and any proteinuria should raise the suspicion of cystic fibrosis-related renal disease.
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Affiliation(s)
- Baha A Al-Shawwa
- Department of Pediatrics, Medical College of Wisconsin (Pulmonary Section), Children's Hospital of Wisconsin, 9000 West Wisconsin Avenue, MS # B620, Milwaukee, WI 53226, USA
| | - Aparna R Rao
- Department of Pediatrics, Medical College of Wisconsin (Pulmonary Section), Children's Hospital of Wisconsin, 9000 West Wisconsin Avenue, MS # B620, Milwaukee, WI 53226, USA
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Orive Olondriz B, Elorz Lambarri J, Vázquez Cordero C. [Nephrolitiasis in a patient with cystic fibrosis]. An Pediatr (Barc) 2006; 65:154-7. [PMID: 16948978 DOI: 10.1157/13091485] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Defects in the CFTR gene cause abnormal chloride conductance across the apical membrane of epithelial cells, which results in progressive lung disease and also affects other organs. Because life expectancy has increased, other complications of CF have become more apparent. We present a patient with CF and symptomatic nephrolithiasis. Several stones were evident in both kidneys. A 24-hour urine sample showed hyperoxaluria (141 mg/24 h/ 1.73 m(2)) and hypocitraturia and (206 mg/24 h/1.73 m(2), 177 mg citrate/g creatinine). Nephrolithiasis should be included in the differential diagnosis of patients with CF and abdominal pain; urinary excretion of oxalate and citrate should be investigated.
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Terribile M, Capuano M, Cangiano G, Carnovale V, Ferrara P, Petrarulo M, Marangella M. Factors increasing the risk for stone formation in adult patients with cystic fibrosis. Nephrol Dial Transplant 2006; 21:1870-5. [PMID: 16595587 DOI: 10.1093/ndt/gfl067] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND Patients with cystic fibrosis (CF) are at high risk of nephrolithiasis (NL), but controversy still exists in terms of causes, including low urine output, hypercalciuria, hyperoxaluria, hyperuricosuria and hypocitraturia. Moreover, heterozygotes (H-CF), which may exhibit altered renal concentrating and diluting ability, have never studied so far. We, therefore, evaluated the metabolic and physicochemical data of adult CF and H-CF patients, comparing them to controls (C). METHODS Twenty-nine CF patients (16 females, aged 28.4 +/- 7.1 years), 20 H-CF (12 females, aged 58.6 +/- 6.3 years) and 30 C (19 females, aged 39.1 +/- 11.5 years) underwent kidney ultrasound and metabolic evaluation to assess stone risk profile. RESULTS There was a 21% prevalence of NL in CF vs 15% in H-CF. The CF group had elevated uric acid, but no other serological differences compared with the H-CF and C group. Conversely, the citrate and oxalate content in the urine differed significantly, being lower and higher, respectively. These changes held after correction for urine creatinine. Consequently, urine specimens were more supersaturated with calcium oxalate, despite exhibiting no differences for other relevant constituents. Uric acid increased only after normalization for the body weight and urine creatinine. Lower urine volume and more acidic pH produced mild supersaturation with uric acid in samples from CF, while urine from both H-CF and C remained undersaturated. H-CF had only minor increases in both urine oxalate and calcium oxalate supersaturation. CONCLUSIONS This study confirms a high prevalence of kidney stones among CF patients associated with supersaturated urine. Their longer survival justifies diets and/or medications aimed at reducing the risk of forming stones.
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Affiliation(s)
- Maurizio Terribile
- Department of Nephrology and Renal Stone Centre, Pellgrini Hospital Napoli, Italy.
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Hoppe B, von Unruh G, Laube N, Hesse A, Sidhu H. Oxalate degrading bacteria: new treatment option for patients with primary and secondary hyperoxaluria? ACTA ACUST UNITED AC 2005; 33:372-5. [PMID: 16284877 DOI: 10.1007/s00240-005-0497-z] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2005] [Accepted: 06/28/2005] [Indexed: 10/25/2022]
Abstract
Current treatment options in patients with primary and secondary hyperoxaluria are limited and do not always lead to sufficient reduction in urinary oxalate excretion. Intestinal oxalate degrading bacteria are capable of degrading oxalate to CO(2) and formate, the latter being further metabolized and excreted via the feces. It is speculated, that both endogenously produced, as well as dietary oxalate can be significantly removed via the intestinal tract. Oxalobacter formigenes, an obligate anaerobic microbe normally found in the intestinal tract has one oxalate degrading enzyme, oxalyl-CoA decarboxylase, which is also found in Bifidobacterium lactis. Other bacteria with possible oxalate degrading potency are lactic acid bacteria, as well as Enterococcus faecalis and Eubacterium lentum. However, specific therapeutic studies on humans are scarce and, except for Oxalobacter, data are not congruent. We found the oral application of Oxalobacter successful in patients with primary hyperoxaluria. However, long-term post-treatment follow-up of 1-2 years showed that constant intestinal colonization is not achieved in most patients. In one patient with constant colonization, urinary oxalate excretion normalized over time. Short-term studies with other bacteria such as lactic acid bacteria did not show a specific reduction in urinary oxalate excretion. O. formigenes might be a promising new therapeutic tool in patients with primary and secondary hyperoxaluria.
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Affiliation(s)
- Bernd Hoppe
- University Children's Hospital Cologne, Division of Pediatric Nephrology, University of Cologne, Kerpenerstrasse 62, 50931 Cologne, Germany.
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Hoppe B, von Unruh GE, Blank G, Rietschel E, Sidhu H, Laube N, Hesse A. Absorptive hyperoxaluria leads to an increased risk for urolithiasis or nephrocalcinosis in cystic fibrosis. Am J Kidney Dis 2005; 46:440-5. [PMID: 16129205 DOI: 10.1053/j.ajkd.2005.06.003] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2005] [Accepted: 06/06/2005] [Indexed: 12/21/2022]
Abstract
BACKGROUND Hyperoxaluria has been incriminated to account for the increased incidence of urolithiasis or nephrocalcinosis in patients with cystic fibrosis (CF). Hyperoxaluria presumably is caused by fat malabsorption and the absence of such intestinal oxalate-degrading bacteria as Oxalobacter formigenes. To better elucidate its pathophysiological characteristics, we prospectively studied patients with CF by determining these parameters and performing renal ultrasonography twice yearly. METHODS In addition to routine tests in urine (lithogenic and stone-inhibitory substances), the presence of O formigenes was tested in stool, plasma oxalate was measured, and a [13C2]oxalate absorption test was performed in 37 patients with CF aged 5 to 37 years (15 females, 22 males) who were constantly hyperoxaluric before the study. RESULTS Hyperoxaluria (oxalate, 46 to 141 mg/1.73 m2/24 h [0.51 to 1.57 mmol/1.73 m2/24 h]; normal, < 45 mg/1.73 m2/24 h [< 0.5 mmol/1.73 m2/24 h]) was now found in 24 patients (64.8%). Plasma oxalate levels were elevated in 6 patients (7.92 to 19.5 micromol/L; normal, 6.3 +/- 1.1 micromol/L). Oxalobacter species were detected in only 1 patient. Intestinal oxalate absorption was elevated (11.4% to 28.5%; normal, < 10%) in 23 patients. Hypocitraturia was present in 17 patients (citrate, 0.35 to 2.8 g/1.73 m2/24 h [0.2 to 1.1 mmol/1.73 m2/24 h]; normal female, > 2.8 mg/1.73 m2/24 h [> 1.6 mmol/1.73 m2/24 h]; male, > 3.3 mg/1.73 m2/24 h [> 1.9 mmol/1.73 m2/24 h]). Urine calcium oxalate saturation was elevated in 17 patients (5.62 to 28.9 relative units; normal female, < 5.5 relative units; male, < 6.3 relative units). In 16% of patients, urolithiasis (n = 2) or nephrocalcinosis (n = 4) was diagnosed ultrasonographically. CONCLUSION Absorptive hyperoxaluria and hypocitraturia are the main culprits for the increased incidence of urolithiasis and nephrocalcinosis in patients with CF. We advocate high fluid intake, low-oxalate/high-calcium diet, and alkali citrate medication, if necessary. Additional studies are necessary to determine the influence of Oxalobacter species or other oxalate-degrading bacteria on oxalate handling in patients with CF.
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Affiliation(s)
- Bernd Hoppe
- University Children's Hospital Cologne, Germany, USA.
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Al-Aloul M, Miller H, Alapati S, Stockton PA, Ledson MJ, Walshaw MJ. Renal impairment in cystic fibrosis patients due to repeated intravenous aminoglycoside use. Pediatr Pulmonol 2005; 39:15-20. [PMID: 15521084 DOI: 10.1002/ppul.20138] [Citation(s) in RCA: 128] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Although there are reports of cases of acute renal failure occurring in cystic fibrosis (CF) patients, usually in association with the use of nephrotoxic antibiotic therapy, there have been no studies of renal function in this patient group. We hypothesized that long-term use of intravenous (IV) nephrotoxic antibiotics (aminoglycosides and colistin sulphomethate) may contribute to renal disease in CF patients. In a prospective study, we assessed creatinine clearance as an index of renal function with two techniques (24-hr urine collections and the Cockroft-Gault formula) in a group of 80 stable adult CF outpatients chronically infected with Pseudomonas aeruginosa but with no history of preceding renal disease. Using a multiple linear regression model, we evaluated their renal function in terms of their lifetime IV use of aminoglycosides and colistin. Between 31% (Cockroft-Gault formula method) and 42% (24-hr urine collection method) of patients had a creatinine clearance below normal range. Using either method, there was a strong correlation between aminoglycoside use and diminishing renal function (r=- 0.32, P=0.0055), which was potentiated by the coadministration of colistin (r=- 0.42, P <0.0002). However, there was no correlation with colistin when used in combination with other antibiotics alone (r=0.18, P=NS). Repeated IV aminoglycoside use in CF is associated with long-term renal damage. Although this effect is potentiated by colistin, colistin on its own in moderate doses does not appear to be nephrotoxic. IV aminoglycosides should be used cautiously in CF patients, with regular monitoring of renal function.
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Affiliation(s)
- M Al-Aloul
- Adult Cystic Fibrosis Unit, Cardiothoracic Center, Liverpool, UK
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Abstract
The prevalence of urolithiasis is higher in patients with cystic fibrosis than in the normal population. We report on a case of a 12-year-old child with cystic fibrosis who presented flank pain which revealed a calcium oxalate urolithiasis. Evolution was satisfactory with pharmacological and dietary treatment. The principal mechanisms of lithogenesis in patients with cystic fibrosis are described and preventive treatment is discussed.
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Affiliation(s)
- S Nathanson
- Service de pédiatrie-néonatologie, hôpital André-Mignot, centre hospitalier de Versailles, 177, rue de Versailles, 78157 Le Chesnay cedex, France.
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Abstract
BACKGROUND There is a growing body of evidence regarding the association between cystic fibrosis (CF) and nephrolithiasis and the role that Oxalobacter formigenes may have in that association. METHODS We performed a MEDLINE search of "cystic fibrosis and nephrolithiasis" and "Oxalobacter formigenes." Epidemiological and experimental evidence and possible mechanisms explaining the association were critically reviewed. RESULTS Of patients with CF, 3.0% to 6.3% are affected with nephrolithiasis, a percentage greater than that of age-matched controls without CF, in whom the rate is 1% to 2%. Studies have suggested possible mechanisms for the association, including hyperuricosuria, hyperoxaluria, primary defects in calcium handling caused by mutation of the CF transmembrane regulator (CFTR), hypocitraturia, and lack of colonization with O formigenes, an enteric oxalate-degrading bacterium. The absence of colonization could be related to frequent courses of antibiotics. CONCLUSION Although the incidence of stones in patients with CF may be increased compared with controls without CF, many possible mechanisms are implicated. The relative contributions of these mechanisms remain uncertain. Future directions may include specific identification of lithogenic risks and therapy aimed at stone prevention in this population.
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Affiliation(s)
- Eric M Gibney
- University of Colorado Health Sciences Center, Denver, CO, USA
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Perez-Brayfield MR, Caplan D, Gatti JM, Smith EA, Kirsch AJ. Metabolic risk factors for stone formation in patients with cystic fibrosis. J Urol 2002; 167:480-4. [PMID: 11792901 DOI: 10.1097/00005392-200202000-00007] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE Cystic fibrosis is characterized by chronic pulmonary disease, insufficient pancreatic and digestive function, and abnormal sweat concentrations. Patients with cystic fibrosis also have an increased incidence of nephrolithiasis. We compared the results of metabolic evaluation in patients with cystic fibrosis with and without nephrolithiasis. MATERIALS AND METHODS A total of 496 patients were evaluated at our center, including 98 with a mean age of 25 years who had cystic fibrosis and complete metabolic evaluation available between 1996 and 2000. Of these patients 13 (13%) had a history of nephrolithiasis. The records were reviewed for clinical characteristics and all patients underwent metabolic evaluation, including serum electrolyte measurement and 24-hour urine collection. Statistical analysis was done to compare the stone versus nonstone groups. RESULTS The incidence of nephrolithiasis in our study was 3%. We identified 13 patients 16 to 41 years old (mean age 27) with nephrolithiasis, of whom 62% had had multiple episodes. Flank pain was the presenting symptom in 9 of the 13 cases (69%). Renal ultrasound and computerized tomography were the most common imaging modalities. In 9 cases stones were passed without intervention, extracorporeal shock wave lithotripsy was required in 2 and ureteroscopy with stone extraction was done in 2. Calcium oxalate was the dominant stone composition in the 9 patients in whom stone analysis was performed. Metabolic evaluation of the stone versus no stone groups showed elevated urinary oxalate (45.5 versus 42.5 mg./24 hours), relative calcium oxalate supersaturation (5.3 versus 7.2) and decreased urinary citrate in the 2 groups. There was a statistical difference in citrate excretion with lower levels in stone formers (102 versus 218 mg./24 hours, p = 0.0007). CONCLUSIONS Patients with cystic fibrosis have an increased incidence of nephrolithiasis and are at high risk for recurrence. Metabolic evaluation is indicated in all patients with cystic fibrosis and urolithiasis since most have hyperoxaluria, urinary calcium oxalate supersaturation and decreased urinary citrate. Correcting detected stone risk factors in these cases may decrease stone recurrence.
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Affiliation(s)
- Marcos R Perez-Brayfield
- Division of Pediatric Urology, Department of Urology and Cystic Fibrosis Center, Emory University School of Medicine, Children's Healthcare of Atlanta, Georgia, USA
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Böhles H, Gebhardt B, Beeg T, Sewell AC, Solem E, Posselt G. Antibiotic treatment-induced tubular dysfunction as a risk factor for renal stone formation in cystic fibrosis. J Pediatr 2002; 140:103-9. [PMID: 11815772 DOI: 10.1067/mpd.2002.120694] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
OBJECTIVES Our purpose was to characterize the decisive pathophysiologic factors that lead to renal stone formation (nephrolithiasis) in patients with cystic fibrosis (CF). METHODS Patients with CF (n = 96) were investigated with respect to lithogenic and inhibitory factors of urolithiasis and compared with 30 healthy control patients. They were subdivided into 2 groups, 86 without renal stones and 10 with renal stones. RESULTS All stones were exclusively composed of calcium oxalate. As a major pathogenic factor, a urinary disequilibrium between promoting and inhibitory components of stone formation, characterized mainly by hypercalciuria, hyperoxaluria, and hypocitraturia, was found in the patients with nephrolithiasis. They tended to have lower plasma phosphate concentrations and an increased urinary phosphate excretion. The citrate/calcium ratio proved to be a valuable means to discriminate patients with renal stones from control patients. Patients with stones had ingested more cotrimoxazole and ceftazidim, cumulatively, than patients without stones. There was an inverse correlation between the amounts of antibiotics ingested and the percentage of tubular phosphate reabsorption (r = -0.91, P <.0046). CONCLUSION Renal stone formation in patients with CF is caused by a disequilibrium between promoting and inhibitory components of stone formation, which is dominated by hypercalciuria, hyperoxaluria, and hypocitraturia. Treatment with cotrimoxazole and ceftazidim, primarily, may lead to renal proximal tubular damage with an ensuing sequence of phosphate loss, increase of parathyroid hormone secretion, increased 1,25-dihydroxyvitamin D3 formation, and absorptive hypercalciuria.
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Affiliation(s)
- Hansjosef Böhles
- Department of Pediatrics, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany
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Schindler R, Radke C, Paul K, Frei U. Renal problems after lung transplantation of cystic fibrosis patients. Nephrol Dial Transplant 2001; 16:1324-8. [PMID: 11427619 DOI: 10.1093/ndt/16.7.1324] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- R Schindler
- Department of Nephrology and Internal Intensive Care Medicine, Universitätsklinikum Charité, Campus Virchow Klinikum, Berlin, Germany
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Sidhu H, Hoppe B, Hesse A, Tenbrock K, Brömme S, Rietschel E, Peck AB. Absence of Oxalobacter formigenes in cystic fibrosis patients: a risk factor for hyperoxaluria. Lancet 1998; 352:1026-9. [PMID: 9759746 DOI: 10.1016/s0140-6736(98)03038-4] [Citation(s) in RCA: 188] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND Patients with cystic fibrosis have an increased risk of hyperoxaluria, and of subsequent nephrocalcinosis and calcium-oxalate urolithiasis. Oxalate homoeostasis is controlled, in part, by the intestinal bacterium, Oxalobacter formigenes. The loss of this bacterium from the gut flora is associated with an increased risk of hyperoxaluria and calcium-oxalate urolithiasis. We investigated whether the absence of O. formigenes and the presence of hyperoxaluria are correlated in cystic fibrosis (CF) patients. METHODS Stool specimens from 43 patients with CF aged 3-9 years and from 21 similarly aged healthy volunteers were examined for O. formigenes by culture and DNA analysis. At the same time, 24 h urine samples were collected and analysed for oxalate and other factors that promote or inhibit stone formation. FINDINGS 15 (71%) of 21 healthy volunteers but only seven (16%) of 43 CF patients were colonised with O. formigenes. Detection of O. formigenes in six of these seven patients required DNA-based identification, suggesting low numbers of colony-forming units, and the CF patient with normal numbers of O. formigenes was the only one of the 43 patients who had not been treated with antibiotics. All seven CF patients colonised with O. formigenes had normal urinary oxalate levels, but 19 (53%) of 36 patients not colonised with O. formigenes were hyperoxaluric, with the most severe hyperoxaluria occurring in young patients. INTERPRETATION Absence of O. formigenes from the intestinal tract of CF patients appears to lead to increased absorption of oxalate, thereby increasing the risk of hyperoxaluria and its complications (eg, nephrocalcinosis, urolithiasis). Prolonged widespread use of antibiotics, and alterations of the gastrointestinal tract that occur in CF, may induce a permanent decolonisation in CF patients.
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Affiliation(s)
- H Sidhu
- Division of Oxalate Research, Ixion Biotechnology, Alachua, FL, USA
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