Systematic assessment of monogenic etiology in adult-onset kidney stone formers undergoing urological intervention-evidence for genetic pretest probability.
Am J Med Genet C Semin Med Genet
; 190(3): 279-288, 2022 09.
Article
em En
| MEDLINE
| ID: mdl-35923129
ABSTRACT
Kidney stone disease (KSD) is a prevalent condition associated with high morbidity, frequent recurrence, and progression to chronic kidney disease (CKD). The etiology is multifactorial, depending on environmental and genetic factors. Although monogenic KSD is frequent in children, unbiased prevalence data of heritable forms in adults is scarce. Within 2 years of recruitment, all patients hospitalized for urological kidney stone intervention at our center were consecutively enrolled for targeted next generation sequencing (tNGS). Additionally, clinical and metabolic assessments were performed for genotype-phenotype analyses. The cohort comprised 155 (66%) males and 81 (34%) females, with a mean age at first stone of 47 years (4-86). The diagnostic yield of tNGS was 6.8% (16/236), with cystinuria (SLC3A1, SLC7A9), distal renal tubular acidosis (SLC4A1), and renal phosphate wasting (SLC34A1, SLC9A3R1) as underlying hereditary disorders. While metabolic syndrome traits were associated with late-onset KSD, hereditary KSD was associated with increased disease severity in terms of early-onset, frequent recurrence, mildly impaired kidney function, and common bilateral affection. By employing systematic genetic analysis to a less biased cohort of common adult kidney stone formers, we demonstrate its diagnostic value for establishing the underlying disorder in a distinct proportion. Factors determining pretest probability include age at first stone (<40 years), frequent recurrence, mild CKD, and bilateral KSD.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cálculos Renais
/
Insuficiência Renal Crônica
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
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Risk_factors_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
Am J Med Genet C Semin Med Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Alemanha