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Current Urology Reports May 2014Over the past 10 years, a variety of reports have linked bariatric surgery to metabolic changes that alter kidney stone risk. Most of these studies were retrospective,... (Review)
Review
Over the past 10 years, a variety of reports have linked bariatric surgery to metabolic changes that alter kidney stone risk. Most of these studies were retrospective, lacked appropriate controls, or involved bariatric patients with a variety of inclusion criteria. Despite these limitations, recent clinical and experimental research has contributed to our understanding of the pathophysiology of stone disease in this high-risk population. This review summarizes the urinary chemistry profiles that may be responsible for the increased kidney stone incidence seen in contemporary epidemiological bariatric studies, outlines the mechanisms of hyperoxaluria and potential therapies through a newly described experimental bariatric animal model, and provides a focused appraisal of recommendations for reducing stone risk in bariatric stone formers.
Topics: Bariatric Surgery; Global Health; Humans; Hyperoxaluria; Incidence; Kidney Calculi; Obesity, Morbid; Postoperative Complications; Risk Factors
PubMed: 24658828
DOI: 10.1007/s11934-014-0401-x -
Nephrology, Dialysis, Transplantation :... Mar 2016Hyperoxaluria is a frequent complication of inflammatory bowel diseases, ileal resection and Roux-en-Y gastric bypass and is well-known to cause nephrolithiasis and... (Review)
Review
Hyperoxaluria is a frequent complication of inflammatory bowel diseases, ileal resection and Roux-en-Y gastric bypass and is well-known to cause nephrolithiasis and nephrocalcinosis. The associated prevalence of chronic kidney disease and end-stage kidney disease (ESKD) is less clear but may be more consequential than recognized. In this review, we highlight three cases of ESKD due to enteric hyperoxaluria following small bowel resections. We review current information on the pathophysiology, complications and treatment of this complex disease.
Topics: Humans; Hyperoxaluria; Kidney Failure, Chronic; Urolithiasis
PubMed: 25701816
DOI: 10.1093/ndt/gfv005 -
Survey of Ophthalmology 1991Several childhood multisystem disorders with prominent ophthalmological manifestations have been ascribed to the malfunction of the peroxisome, a subcellular organelle.... (Review)
Review
Several childhood multisystem disorders with prominent ophthalmological manifestations have been ascribed to the malfunction of the peroxisome, a subcellular organelle. The peroxisomal disorders have been divided into three groups: 1) those that result from defective biogenesis of the peroxisome (Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum's disease); 2) those that result from multiple enzyme deficiencies (rhizomelic chondrodysplasia punctata); and 3) those that result from a single enzyme deficiency (X-linked adrenoleukodystrophy, primary hyperoxaluria type 1). Zellweger syndrome, the most lethal of the three peroxisomal biogenesis disorders, causes infantile hypotonia, seizures, and death within the first year. Ophthalmic manifestations include corneal opacification, cataract, glaucoma, pigmentary retinopathy and optic atrophy. Neonatal adrenoleukodystrophy and infantile Refsum's disease appear to be genetically distinct, but clinically, biochemically, and pathologically similar to Zellweger syndrome, although milder. Rhizomelic chondrodysplasia punctata, a peroxisomal disorder which results from at least two peroxisomal enzyme deficiencies, presents at birth with skeletal abnormalities and patients rarely survive past one year of age. The most prominent ocular manifestation consists of bilateral cataracts. X-linked (childhood) adrenoleukodystrophy, results from a deficiency of a single peroxisomal enzyme, presents in the latter part of the first decade with behavioral, cognitive and visual deterioration. The vision loss results from demyelination of the entire visual pathway, but the outer retina is spared. Primary hyperoxaluria type 1 manifests parafoveal subretinal pigment proliferation. Classical Refsum's disease may also be a peroxisomal disorder, but definitive evidence is lacking. Early identification of these disorders, which may depend on recognizing the ophthalmological findings, is critical for prenatal diagnosis, treatment, and genetic counselling.
Topics: Abnormalities, Multiple; Adrenoleukodystrophy; Animals; Fundus Oculi; Humans; Hyperoxaluria; Metabolism, Inborn Errors; Microbodies; Refsum Disease; Retinal Diseases; Zellweger Syndrome
PubMed: 1710072
DOI: 10.1016/0039-6257(91)90185-i -
Turk Kardiyoloji Dernegi Arsivi : Turk... Sep 2015
Topics: Cardiomyopathies; Ductus Arteriosus, Patent; Humans; Hyperoxaluria, Primary; Male
PubMed: 26363766
DOI: 10.5543/tkda.2015. -
Scientific Reports Sep 2022Primary hyperoxaluria (PH) is an autosomal recessive disorder of oxalate metabolism caused by pathogenic variants in either of three genes (AGXT, GRHPR or HOGA1). The...
Primary hyperoxaluria (PH) is an autosomal recessive disorder of oxalate metabolism caused by pathogenic variants in either of three genes (AGXT, GRHPR or HOGA1). The study aimed at characterizing the clinical phenotypes as well as the genotypic spectrum of PH in Egypt. We screened 25 Egyptian patients suspected of PH for the three responsible genes by Sanger sequencing. We diagnosed 20 patients from 18 unrelated families, in which the natural history, family history, clinical features and genotypes were evaluated. PH patients were 15 males and 5 females ranging in age from 4 months to 31 years (median 8 years). Fifteen families were consanguineous (83%) and familial clustering was reported in six families (33%). Pathogenic variants in all 40 alleles were in AGXT, with none detected in GRHPR or HOGA1. We detected two novel pathogenic variants c.166-1_172dupGATCATGG (p.Asp58Glyfs*65) and c.766delC (p.Gln256fs*16) and seven previously reported variants in our cohort. This is the first study reporting the genotype of a considerable number of PH1 patients from Egypt. Our detected variants in the AGXT gene could form the basis for future genetic counseling and prenatal diagnosis in Egypt and surrounding populations.
Topics: Adolescent; Adult; Child; Child, Preschool; Egypt; Female; Humans; Hyperoxaluria, Primary; Infant; Male; Mutation; Oxalates; Phenotype; Transaminases; Young Adult
PubMed: 36151119
DOI: 10.1038/s41598-022-17980-9 -
BMJ (Clinical Research Ed.) Jun 2004
Review
Topics: Calcium; Citric Acid; Colic; Glycoproteins; Humans; Hyperoxaluria; Kidney Calculi; Magnesium Compounds; Phosphates; Recurrence; Risk Factors; Struvite; Uric Acid
PubMed: 15191979
DOI: 10.1136/bmj.328.7453.1420 -
Urolithiasis Apr 2022Hyperoxaluria, one of the major risk factors for calcium oxalate urolithiasis and nephrocalcinosis, causes significant morbidity and mortality and should therefore be...
Hyperoxaluria, one of the major risk factors for calcium oxalate urolithiasis and nephrocalcinosis, causes significant morbidity and mortality and should therefore be detected and treated as soon as possible. An early, consequent and adequate evaluation, but also a distinction between primary (PH) and secondary hyperoxaluria (SH) is therefore essential. We evaluated the usefulness of three consecutive 24-h urine collections under different diets [usual diet, (A), low oxalate diet, (B), high oxalate diet, (C)] to prove SH, or to find evidence of PH by changes in urinary oxalate excretion (Uox). We retrospectively analyzed results from 96 pediatric patients (47 females and 49 males, age 3-18 years) who presented with a history of nephrolithiasis, nephrocalcinosis and/or persistent hematuria in whom hyperoxaluria was found in an initial urine sample. The typical pattern of SH was found in 34 patients (mean Uox (A) 0.85 ± 0.29, (B) 0.54 ± 0.15 and (C) 0.95 ± 0.28 mmol/1.73m/d). PH was suspected in 13 patients [(A) 1.21 ± 0.75; (B) 1.47 ± 0.51 and (C) 1.60 ± 0.82 mmol/1.73m/d], but genetically proven only in 1/5 patients examined. No hyperoxaluria was found in 16 patients. Data were inconclusive in 33 patients. Urine collection under different diets is helpful to diagnose secondary hyperoxaluria and may provide evidence, that urinary oxalate excretion is normal. We have now established this procedure as our first diagnostic step before further, more extensive and more expensive evaluations are performed.
Topics: Adolescent; Child; Child, Preschool; Diet; Female; Humans; Hyperoxaluria; Kidney Calculi; Male; Oxalates; Retrospective Studies; Urine Specimen Collection
PubMed: 34821949
DOI: 10.1007/s00240-021-01290-2 -
Journal of Pediatric Urology Apr 2021Calcium oxalate stones are the most common type among stone-forming patients and in some cases result from predisposed genetic conditions. In this work, we examined the...
OBJECTIVE
Calcium oxalate stones are the most common type among stone-forming patients and in some cases result from predisposed genetic conditions. In this work, we examined the differences in structure and chemical composition between oxalate stones from patients from three groups: 1) pediatric patients that were genetically predisposed (primary hyperoxaluria) to form stones (PPH); 2) control pediatric patients that did not have such genetic predisposition (PN-PH); 3) adult patients that formed oxalate stones without the genetic predisposition (A-CaOx). A variety of instrumental analyses were conducted to identify physicochemical properties of stones characteristic of predisposed pediatric (PPH), pediatric hyperoxaluria (PN-PH), and adult (A-CaOx) patient populations.
METHODS
Genetic variants of 16 stone-forming patients were determined using whole-exome gene sequencing. Components of stones from PPH (n = 6), PN-PH (n = 5), and A-CaOx (n = 5) groups were identified using Fourier transform infrared (FTIR) spectroscopy. Stone morphology and density were evaluated using high resolution X-ray computed tomography (micro-XCT). Stone microstructure and elemental composition were mapped with scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy, respectively.
RESULTS
Calcium oxalate bipyramidal crystals were found on stones from all groups. Stones from PPH patients with PH types I and II were composed of calcium oxalate monohydrate (COM) with relatively uniform mineral density (1224 ± 277 mg/cc) and distinct smooth surfaces. By contrast, micro-spherical calcium phosphate particles were found only on PN-PH stones, which also showed a broader range of mineral densities (1266 ± 342 mg/cc). Stones from the PN-PH group also contained phosphorus (P), which was absent in NP-PH stones. A-CaOx stones were of significantly lower mineral density (645 ± 237 mg/cc) than pediatric stones and were more heterogeneous in their elemental composition.
CONCLUSION
Unique structural and compositional characteristics were identified in stones from pediatric patients with primary hyperoxaluria. These include the absence of phosphorus, a narrower mineral density distribution, and a uniform elemental composition compared to stones from pediatric patients without the genetic predisposition. Thus, characterization of stones at the macro- and micro-scales in combination with genetic testing of patients can provide insights and accurate diagnosis to develop a treatment plan for effective patient care.
Topics: Adult; Calcium Oxalate; Child; Humans; Hyperoxaluria, Primary; Kidney Calculi; Tomography, X-Ray Computed
PubMed: 33495102
DOI: 10.1016/j.jpurol.2020.11.023 -
International Urology and Nephrology Apr 2019To evaluate the potential of ALLN-177, an orally administered, oxalate-specific enzyme therapy to reduce urine oxalate (UOx) excretion in patients with secondary...
PURPOSE
To evaluate the potential of ALLN-177, an orally administered, oxalate-specific enzyme therapy to reduce urine oxalate (UOx) excretion in patients with secondary hyperoxaluria.
METHODS
Sixteen male and female subjects with both hyperoxaluria and a kidney stone history were enrolled in an open-label study. Subjects continued their usual diets and therapies. During a 3-day baseline period, two 24-h (24-h) urines were collected, followed by a 4-day treatment period with ALLN-177 (7,500 units/meal, 3 × day) when three 24-h urines were collected. The primary endpoint was the change in mean 24-h UOx from baseline. Safety assessments and 24-h dietary recalls were performed throughout.
RESULTS
The study enrolled 5 subjects with enteric hyperoxaluria and 11 with idiopathic hyperoxaluria. ALLN-177 was well tolerated. Overall mean (SD) UOx decreased from 77.7 (55.9) at baseline to 63.7 (40.1) mg/24 h while on ALLN-177 therapy, with the mean reduction of 14 mg/24 h, (95% CI - 23.71, - 4.13). The calcium oxalate-relative urinary supersaturation ratio in the overall population decreased from a mean of 11.3 (5.7) to 8.8 (3.8) (- 2.8; 95% CI - 4.9, - 0.79). This difference was driven by oxalate reduction alone, but not any other urinary parameters. Mean daily dietary oxalate, calcium, and fluid intake recorded by frequent diet recall did not differ by study periods.
CONCLUSION
ALLN-177 reduced 24-h UOx excretion, and was well tolerated. The results of this pilot study provided justification for further investigation of ALLN-177 in patients with secondary hyperoxaluria.
TRIAL REGISTRATION
Clinicaltrials.gov NCT02289755.
Topics: Administration, Oral; Adult; Aged; Carboxy-Lyases; Diet; Enzyme Therapy; Female; Humans; Hyperoxaluria; Kidney Calculi; Male; Middle Aged; Oxalates
PubMed: 30783888
DOI: 10.1007/s11255-019-02098-1 -
Archives of Disease in Childhood Feb 1959
Topics: Child; Humans; Hyperoxaluria; Infant; Metabolic Diseases; Oxalates
PubMed: 13628232
DOI: 10.1136/adc.34.173.60