Journal article : Review
Genetics of kidney stone disease
- Abstract:
- Kidney stone disease (nephrolithiasis) is a common problem that can be associated with alterations in urinary solute composition including hypercalciuria. Studies suggest that the prevalence of monogenic kidney stone disorders, including renal tubular acidosis with deafness, Bartter syndrome, primary hyperoxaluria and cystinuria, in patients attending kidney stone clinics is ∼15%. However, for the majority of individuals, nephrolithiasis has a multifactorial aetiology involving genetic and environmental factors. Nonetheless, the genetic influence on stone formation in these idiopathic stone formers remains considerable and twin studies estimate a heritability of >45% for nephrolithiasis and >50% for hypercalciuria. The contribution of polygenic influences from multiple loci have been investigated by genome-wide association and candidate gene studies, which indicate that a number of genes and molecular pathways contribute to the risk of stone formation. Genetic approaches, studying both monogenic and polygenic factors in nephrolithiasis, have revealed that the following have important roles in the aetiology of kidney stones: transporters and channels; ions, protons and amino acids; the calcium-sensing receptor (a G protein-coupled receptor) signalling pathway; and the metabolic pathways for vitamin D, oxalate, cysteine, purines and uric acid. These advances, which have increased our understanding of the pathogenesis of nephrolithiasis, will hopefully facilitate the future development of targeted therapies for precision medicine approaches in patients with nephrolithiasis.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
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(Preview, Accepted manuscript, 814.4KB, Terms of use)
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- Publisher copy:
- 10.1038/s41585-020-0332-x
Authors
- Publisher:
- Nature Research
- Journal:
- Nature Reviews Urology More from this journal
- Volume:
- 17
- Issue:
- 7
- Pages:
- 407-421
- Publication date:
- 2020-07-01
- Acceptance date:
- 2020-05-04
- DOI:
- EISSN:
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1759-4820
- ISSN:
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1759-4812
- Pmid:
-
32533118
- Language:
-
English
- Keywords:
- Subtype:
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Review
- Pubs id:
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1113025
- Local pid:
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pubs:1113025
- Deposit date:
-
2020-07-23
Terms of use
- Copyright holder:
- Howles and Thakker.
- Copyright date:
- 2020
- Rights statement:
- © the Author(s) 2020.
- Notes:
- This is the accepted manuscript version of the article. The final version is available from Nature Research at: https://doi.org/10.1038/s41585-020-0332-x
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