Multiomics Assessment of the Gut Microbiome in Rare Hyperoxaluric Conditions.

Introduction: Hyperoxaluria is a risk factor for kidney stone formation and chronic kidney disease progression. The microbiome is an important protective factor against oxalate accumulation through the activity of its oxalate-degrading enzymes (ODEs). In this cross-sectional study, we leverage multiomics to characterize the microbial community of participants with primary and enteric hyperoxaluria, as well as idiopathic calcium oxalate kidney stone (CKS) formers, focusing on the relationship between oxalate degrading functions of the microbiome.

Natural history of urine and plasma oxalate in children with primary hyperoxaluria type 1.

Background: Primary hyperoxaluria type 1 (PH1) is a rare, severe genetic disease causing increased hepatic oxalate production resulting in urinary stone disease, nephrocalcinosis, and often progressive chronic kidney disease. Little is known about the natural history of urine and plasma oxalate values over time in children with PH1.

Methods: For this retrospective observational study, we analyzed data from genetically confirmed PH1 patients enrolled in the Rare Kidney Stone Consortium PH Registry between 2003 and 2018 who had at least 2 measurements before age 18 years of urine oxalate-to-creatinine ratio (Uox:cr), 24-h urine oxalate excretion normalized to body surface area (24-h Uox), or plasma oxalate concentration (Pox).

Comprehensive Genetic Analysis Reveals Complexity of Monogenic Urinary Stone Disease.

Introduction: Because of phenotypic overlap between monogenic urinary stone diseases (USD), gene-specific analyses can result in missed diagnoses. We used targeted next generation sequencing (tNGS), including known and candidate monogenic USD genes, to analyze suspected primary hyperoxaluria (PH) or Dent disease (DD) patients genetically unresolved (negative; N) after Sanger analysis of the known genes. Cohorts consisted of 285 PH (PHN) and 59 DD (DDN) families.

Natural History of Clinical, Laboratory, and Echocardiographic Parameters of a Primary Hyperoxaluria Cohort on Long Term Hemodialysis.

Primary hyperoxaluria type 1 (PH1) is a rare monogenic disorder characterized by excessive hepatic production of oxalate leading to recurrent nephrolithiasis, nephrocalcinosis, and progressive kidney damage, often requiring renal replacement therapy (RRT). Though systemic oxalate deposition is well-known, the natural history of PH1 during RRT has not been systematically described. In this study, we describe the clinical, laboratory, and echocardiographic features of a cohort of PH1 patients on RRT.

Clinical characterization of primary hyperoxaluria type 3 in comparison with types 1 and 2.

Background: Primary hyperoxaluria (PH) type 3 (PH3) is caused by mutations in the hydroxy-oxo-glutarate aldolase 1 gene. PH3 patients often present with recurrent urinary stone disease in the first decade of life, but prior reports suggested PH3 may have a milder phenotype in adults. This study characterized clinical manifestations of PH3 across the decades of life in comparison with PH1 and PH2.

Recovery From Dialysis in Patients With Primary Hyperoxaluria Type 1 Treated With Pyridoxine: A Report of 3 Cases.

Primary hyperoxaluria type 1 (PH1) is a genetic disorder characterized by overproduction of oxalate and eventual kidney failure. Kidney failure is usually irreversible in PH1. However, in patients with PH1 homozygous for the G170R mutation (in which the glycine at amino acid 170 is replaced by an arginine), pyridoxine is an enzyme cofactor and decreases urinary oxalate excretion by reducing hepatic oxalate production.

Clinical features of genetically confirmed patients with primary hyperoxaluria identified by clinical indication versus familial screening.

Primary hyperoxaluria is a rare monogenic disorder characterized by excessive hepatic production of oxalate leading to recurrent nephrolithiasis, nephrocalcinosis, and progressive kidney damage. Most patients with primary hyperoxaluria are diagnosed after clinical suspicion based on symptoms. Since some patients are detected by family screening following detection of an affected family member, we compared the clinical phenotype of these two groups.

Predictors of Incident ESRD among Patients with Primary Hyperoxaluria Presenting Prior to Kidney Failure.

Background And Objectives: Overproduction of oxalate in patients with primary hyperoxaluria (PH) leads to calcium oxalate deposition in the kidney and ESRD in a substantial number of cases. However, the key determinants for renal outcome remain unclear. Thus, we performed a retrospective analysis to identify predictors for renal outcome among patients with PH participating in the Rare Kidney Stone Consortium (RKSC) PH Registry.

Phenotype-Genotype Correlations and Estimated Carrier Frequencies of Primary Hyperoxaluria.

Primary hyperoxaluria (PH) is a rare autosomal recessive disease characterized by oxalate accumulation in the kidneys and other organs. Three loci have been identified: AGXT (PH1), GRHPR (PH2), and HOGA1 (PH3). Here, we compared genotype to phenotype in 355 patients in the Rare Kidney Stone Consortium PH registry and calculated prevalence using publicly available whole-exome data.

Primary hyperoxaluria type III gene HOGA1 (formerly DHDPSL) as a possible risk factor for idiopathic calcium oxalate urolithiasis.

Background And Objectives: Primary hyperoxaluria types I and II (PHI and PHII) are rare monogenic causes of hyperoxaluria and calcium oxalate urolithiasis. Recently, we described type III, due to mutations in HOGA1 (formerly DHDPSL), hypothesized to cause a gain of mitochondrial 4-hydroxy-2-oxoglutarate aldolase activity, resulting in excess oxalate.

Design, Setting, Participants, & Measurements: To further explore the pathophysiology of HOGA1, we screened additional non-PHI-PHII patients and performed reverse transcription PCR analysis.

Relation of bowel habits to fecal incontinence in women.

Background: Though most women with fecal incontinence (FI) have anorectal dysfunctions, a majority have intermittent symptoms. Variations in bowel habits and daily routine may partly explain this.

Aim: To compare bowel habits and daily routine between controls and FI, and between continent and incontinent stools among women with FI.

Insights into normal and disordered bowel habits from bowel diaries.

Background: While symptom questionnaires provide a snapshot of bowel habits, they may not reflect day-to-day variations or the relationship between bowel symptoms and stool form.

Aim: To assess bowel habits by daily diaries in women with and without functional bowel disorders.

Method: From a community-based survey among Olmsted County, MN, women, 278 randomly selected subjects were interviewed by a gastroenterologist, who completed a bowel symptom questionnaire.

Nitrergic contribution to gastric relaxation induced by glucagon-like peptide-1 (GLP-1) in healthy adults.

The incretin glucagon-like peptide-1 (GLP-1), which is used to treat diabetes mellitus, delays gastric emptying by inhibiting vagal activity. GLP-1 also increases fasting and postprandial gastric volume in humans. On the basis of animal studies, we hypothesized that nitric oxide mediates the effects of GLP-1 on gastric volumes.

Risk factors for fecal incontinence: a population-based study in women.

Background: In women with "idiopathic" fecal incontinence (FI), consensus guidelines recommend anal sphincter imaging and surgical repair, when feasible, of anal sphincter defects believed to cause FI. However, the relative contributions of obstetric trauma and bowel symptoms to FI in the community are unknown.

Methods: To assess risk factors for FI during the past year, a previously validated questionnaire was mailed to an age-stratified random sample of 5,300 women residing in Olmsted County, Minnesota.

Differences between painless and painful constipation among community women.

Background: In the Rome II criteria, patients with both constipation and abdominal pain (AP) (i.e., "painful constipation" (PC)), who do not satisfy criteria for irritable bowel syndrome (IBS) are included in the same functional constipation (FC) category as patients with constipation without AP (i.

Comparison of rectoanal axial forces in health and functional defecatory disorders.

Anal manometry measures circumferential pressures but not axial forces that are responsible for defecation and contribute to fecal continence. Our aims were to investigate these mechanisms by measuring axial rectoanal forces with an intrarectal sphere or a latex balloon fixed at 8, 6, or 4 cm from the anal verge and connected to axial force and displacement transducers. Rectoanal forces and rectal pressures within a latex balloon were measured at baseline (i.

Prevalence and burden of fecal incontinence: a population-based study in women.

Background & Aims: The epidemiology of fecal incontinence (FI) is incompletely understood. We report the prevalence, clinical spectrum, health care-seeking behavior, and quality of life (QOL) in community women with FI.

Methods: A questionnaire was mailed to an age-stratified random sample of 5300 Olmsted County, Minnesota, women identified by the Rochester Epidemiology Project.