Urinary stone composition in Germany: results from 45,783 stone analyses.
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ABSTRACT: Purpose
Stone composition can provide valuable information for the diagnosis, treatment and recurrence prevention of urolithiasis. The aim of this study was to evaluate the distribution of urinary stone components and the impact of different crystal forms according to gender and age of patients in Germany.Methods
A total of 45,783 urinary stones submitted from 32,512 men and 13,271 women between January 2007 and December 2020 were analyzed by infrared spectroscopy. Only the first calculus obtained per patient was included in the analysis.Results
The most common main stone component was calcium oxalate (CaOx) (71.4%), followed by carbonate apatite (CA) (10.2%) and uric acid (UA) (8.3%). Struvite (2.1%), brushite (1.3%), protein (0.5%) and cystine (0.4%) stones were only rarely diagnosed. CaOx (75%) and UA stones (81%) were more frequently obtained from men than women (p < 0.001). Weddellite (COD) and uric acid dihydrate (UAD) were more common in younger ages than whewellite (COM) and anhydrous uric acid (UAA), respectively, in both men and women. The ratios of COM-to-COD and UAA-to-UAD calculi were approximately 4:1 and 8:1, respectively. The peak of stone occurrence was between the ages of 40 and 59 years.Conclusion
Stone composition is strongly associated with gender and age. The peak incidence of calculi in both women and men was in the most active phase of their working life. The distinction between different crystal forms could provide clues to the activity and mechanisms of lithogenesis. Further research is needed in understanding the causative factors and the process of stone formation.
SUBMITTER: Siener R
PROVIDER: S-EPMC9236976 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionBecause 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.MethodsVariants were assessed using disease-specific and population databases plus variant assessment tools and categorized using the American College of Medical Genetics (ACMG) guidelines. Prior Sanger analysis identified 47 novel PH or DD gene pathogenic variants.ResultsScreening by tNGS revealed pathogenic variants in 14 known monogenic USD genes, accounting for 45 families (13.1%), 27 biallelic and 18 monoallelic, including 1 family with a copy number variant (CNV). Recurrent genes included the following: SLC34A3 (n = 13), CLDN16 (n = 8), CYP24A1 (n = 4), SLC34A1 (n = 3), SLC4A1 (n = 3), APRT (n = 2), CLDN19 (n = 2), HNF4A1 (n = 2), and KCNJ1 (n = 2), whereas ATP6V1B1, CASR, and SLC12A1 and missed CNVs in the PH genes AGXT and GRHPR accounted for 1 pedigree each. Of the 48 defined pathogenic variants, 27.1% were truncating and 39.6% were novel. Most patients were diagnosed before 18 years of age (76.1%), and 70.3% of biallelic patients were homozygous, mainly from consanguineous families.ConclusionOverall, in patients suspected of DD or PH, 23.9% and 7.3% of cases, respectively, were caused by pathogenic variants in other genes. This study shows the value of a tNGS screening approach to increase the diagnosis of monogenic USD, which can optimize therapies and facilitate enrollment in clinical trials.
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Project description:BackgroundIncreased urinary exosomes are associated with kidney stones but how they work is unknown. In this study, we aim to identify dysregulated proteins in urinary exosomes from kidney stone patients and to explore the potential role of exosomal proteins in nephrolithiasis.MethodsFirst morning voids were collected from participants. Urinary exosomes were isolated via ultracentrifugation. Label free liquid chromatography-tandem mass spectrometry was performed to analyze the proteome of urine exosomes from three kidney stone patients and three age-/sex-matched healthy controls. Bioinformatics analysis was conducted to identify dysregulated proteins associated with stone formation. Results of proteomic analysis were verified by Western blotting in other three kidney stone patients and three healthy controls.ResultsNine hundred and sixty proteins were identified with proteomic analysis, of which 831 were identified in the control group and 879 in the stone group. Sixteen proteins in urinary exosomes were found most significantly different between kidney stone patients and healthy controls. Gene ontology (GO) analysis showed that dysregulated proteins were enriched in innate immune response, defense response to bacterium and calcium-binding. S100A8, S100A9 and S100A12 were common in above three GO terms and were chosen for further study. Western blotting confirmed that the expression of these three S100 proteins was higher in urinary exosomes from kidney stone patients. In addition, S100 proteins were aggregated in urinary exosomes and it was difficult to detect them in urine.ConclusionsUrinary exosomes from kidney stone patients are rich in S100 proteins and play a role in innate immune response, defense response to bacterium and calcium-binding.
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