Skip to main content
SpringerLink
Log in

Identification of mutations in 15 nephrolithiasis-related genes leading to a molecular diagnosis in 85 Chinese pediatric patients

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Background

The aim of this study was to describe the genotypic and phenotypic characteristics of Chinese pediatric patients with hereditary nephrolithiasis.

Methods

Whole-exome sequencing (WES) was performed on 218 Chinese pediatric patients with kidney stones, and genetic and clinical data were collected and analyzed retrospectively.

Results

The median age at onset in our cohort was 2.5 years (age range, 0.3–13 years). We detected 79 causative mutations in 15 genes, leading to a molecular diagnosis in 38.99% (85/218) of all cases. Monogenic mutations were present in 80 cases, and digenic mutations were present in 5 cases; 34.18% (27/79) of mutations were not included in the databases. Six common mutant genes, i.e., HOGA1, AGXT, GRHPR, SLC3A1, SLC7A9, and SLC4A1, were found in 84.71% of the patients overall. Furthermore, three mutations (A278A, c.834_834 + 1GG > TT, and C257G) in HOGA1, two mutations (K12QfX156 and S275RfX28) in AGXT, and one mutation (C289DfX22) in GRHPR represented hotspot mutations. The patients with HOGA1 mutations had the earliest onset age (0.8 years), followed by those with SLC7A9 (1.8 years), SLC4A1 (2.7 years), AGXT (4.3 years), SLC3A1 (4.8 years), and GRHPR (8 years) mutations (p = 0.002). Nephrocalcinosis was most commonly observed in patients with AGXT gene mutations.

Conclusions

Fifteen causative genes were detected in 85 Chinese pediatric patients with kidney stone diseases. The most common mutant genes, novel mutations, hotspot mutations, and genotype–phenotype correlations were also found. This study contributes to the understanding of genetic profiles and clinical courses in pediatric patients with hereditary nephrolithiasis.

Graphical abstract

A higher resolution version of the Graphical abstract is available as Supplementary information

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Singh P, Harris PC, Sas DJ, Lieske JC (2022) The genetics of kidney stone disease and nephrocalcinosis. Nat Rev Nephrol 18:224–240. https://doi.org/10.1038/s41581-021-00513-4

    Article  PubMed  Google Scholar 

  2. Wang W, Fan J, Huang G, Li J, Zhu X, Tian Y, Su L (2017) Prevalence of kidney stones in mainland China: a systematic review. Sci Rep 7:41630. https://doi.org/10.1038/srep41630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Howles SA, Thakker RV (2020) Genetics of kidney stone disease. Nat Rev Urol 17:407–421. https://doi.org/10.1038/s41585-020-0332-x

    Article  PubMed  Google Scholar 

  4. Miah T, Kamat D (2017) Pediatric nephrolithiasis: a review. Pediatr Ann 46:e242–e244. https://doi.org/10.3928/19382359-20170517-02

    Article  PubMed  Google Scholar 

  5. Zhao Y, Fang X, Fan Y, Sun Y, He L, Xu M, Xu G, Li Y, Huang Y, Yu Y, Geng H (2021) Integration of exome sequencing and metabolic evaluation for the diagnosis of children with urolithiasis. World J Urol 39:2759–2765. https://doi.org/10.1007/s00345-020-03449-9

    Article  CAS  PubMed  Google Scholar 

  6. Halbritter J (2021) Genetics of kidney stone disease-polygenic meets monogenic. Nephrol Ther 17S:S88–S94. https://doi.org/10.1016/j.nephro.2020.02.003

    Article  PubMed  Google Scholar 

  7. Halbritter J, Baum M, Hynes AM, Rice SJ, Thwaites DT, Gucev ZS, Fisher B, Spaneas L, Porath JD, Braun DA, Wassner AJ, Nelson CP, Tasic V, Sayer JA, Hildebrandt F (2015) Fourteen monogenic genes account for 15% of nephrolithiasis/nephrocalcinosis. J Am Soc Nephrol 26:543–551. https://doi.org/10.1681/ASN.2014040388

    Article  CAS  PubMed  Google Scholar 

  8. Braun DA, Lawson JA, Gee HY, Halbritter J, Shril S, Tan W, Stein D, Wassner AJ, Ferguson MA, Gucev Z, Fisher B, Spaneas L, Varner J, Sayer JA, Milosevic D, Baum M, Tasic V, Hildebrandt F (2016) Prevalence of monogenic causes in pediatric patients with nephrolithiasis or nephrocalcinosis. Clin J Am Soc Nephrol 11:664–672. https://doi.org/10.2215/CJN.07540715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Daga A, Majmundar AJ, Braun DA, Gee HY, Lawson JA, Shril S, Jobst-Schwan T, Vivante A, Schapiro D, Tan W, Warejko JK, Widmeier E, Nelson CP, Fathy HM, Gucev Z, Soliman NA, Hashmi S, Halbritter J, Halty M, Kari JA, El-Desoky S, Ferguson MA, Somers MJG, Traum AZ, Stein DR, Daouk GH, Rodig NM, Katz A, Hanna C, Schwaderer AL, Sayer JA, Wassner AJ, Mane S, Lifton RP, Milosevic D, Tasic V, Baum MA, Hildebrandt F (2018) Whole exome sequencing frequently detects a monogenic cause in early onset nephrolithiasis and nephrocalcinosis. Kidney Int 93:204–213. https://doi.org/10.1016/j.kint.2017.06.025

    Article  CAS  PubMed  Google Scholar 

  10. Cogal AG, Arroyo J, Shah RJ, Reese KJ, Walton BN, Reynolds LM, Kennedy GN, Seide BM, Senum SR, Baum M, Erickson SB, Jagadeesh S, Soliman NA, Goldfarb DS, Beara-Lasic L, Edvardsson VO, Palsson R, Milliner DS, Sas DJ, Lieske JC, Harris PC (2021) Comprehensive genetic analysis reveals complexity of monogenic urinary stone disease. Kidney Int Rep 6:2862–2884. https://doi.org/10.1016/j.ekir.2021.08.033

    Article  PubMed  PubMed Central  Google Scholar 

  11. Gefen AM, Sethna CB, Cil O, Perwad F, Schoettler M, Michael M, Angelo JR, Safdar A, Amlie-Wolf L, Hunley TE, Ellison JS, Feig D, Zaritsky J (2023) Genetic testing in children with nephrolithiasis and nephrocalcinosis. Pediatr Nephrol. https://doi.org/10.1007/s00467-023-05879-0

    Article  PubMed  Google Scholar 

  12. Ziyadov E, Bisgin A, Deger M, Akdogan N, Izol V, Aridogan IA, Satar N (2021) Determination of the etiology of pediatric urinary stone disease by multigene panel and metabolic screening evaluation. J Pediatr Urol 17(476):e1-476 e7. https://doi.org/10.1016/j.jpurol.2021.03.028

    Article  Google Scholar 

  13. Amar A, Majmundar AJ, Ullah I, Afzal A, Braun DA, Shril S, Daga A, Jobst-Schwan T, Ahmad M, Sayer JA, Gee HY, Halbritter J, Knopfel T, Hernando N, Werner A, Wagner C, Khaliq S, Hildebrandt F (2019) Gene panel sequencing identifies a likely monogenic cause in 7% of 235 Pakistani families with nephrolithiasis. Hum Genet 138:211–219. https://doi.org/10.1007/s00439-019-01978-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Huang L, Qi C, Zhu G, Ding J, Yuan L, Sun J, He X, Wang X (2022) Genetic testing enables a precision medicine approach for nephrolithiasis and nephrocalcinosis in pediatrics: a single-center cohort. Mol Genet Genomics 297:1049–1061. https://doi.org/10.1007/s00438-022-01897-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Rhodes HL, Yarram-Smith L, Rice SJ, Tabaksert A, Edwards N, Hartley A, Woodward MN, Smithson SL, Tomson C, Welsh GI, Williams M, Thwaites DT, Sayer JA, Coward RJ (2015) Clinical and genetic analysis of patients with cystinuria in the United Kingdom. Clin J Am Soc Nephrol 10:1235–1245. https://doi.org/10.2215/CJN.10981114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Abid A, Raza A, Khan AR, Firasat S, Shahid S, Hashmi S, Zafar MN, Sultan S, Khaliq S, Rizvi SA (2023) Primary hyperoxaluria: comprehensive mutation screening of the disease causing genes and spectrum of disease-associated pathogenic variants. Clin Genet 103:53–66. https://doi.org/10.1111/cge.14240

    Article  CAS  PubMed  Google Scholar 

  17. Palazzo V, Provenzano A, Becherucci F, Sansavini G, Mazzinghi B, Orlandini V, Giunti L, Roperto RM, Pantaleo M, Artuso R, Andreucci E, Bargiacchi S, Traficante G, Stagi S, Murer L, Benetti E, Emma F, Giordano M, Rivieri F, Colussi G, Penco S, Manfredini E, Caruso MR, Garavelli L, Andrulli S, Vergine G, Miglietti N, Mancini E, Malaventura C, Percesepe A, Grosso E, Materassi M, Romagnani P, Giglio S (2017) The genetic and clinical spectrum of a large cohort of patients with distal renal tubular acidosis. Kidney Int 91:1243–1255. https://doi.org/10.1016/j.kint.2016.12.017

    Article  CAS  PubMed  Google Scholar 

  18. Gordon RJ, Li D, Doyle D, Zaritsky J, Levine MA (2020) Digenic heterozygous mutations in SLC34A3 and SLC34A1 cause dominant hypophosphatemic rickets with hypercalciuria. J Clin Endocrinol Metab 105:2392–2400. https://doi.org/10.1210/clinem/dgaa217

    Article  PubMed  PubMed Central  Google Scholar 

  19. Abid A (2021) Possible ethnic associations in primary hyperoxaluria type-III-associated HOGA1 sequence variants. Mol Biol Rep 48:3841–3844. https://doi.org/10.1007/s11033-021-06380-3

    Article  CAS  PubMed  Google Scholar 

  20. Abukhatwah MW, Almalki SH, Althobaiti MS, Alharbi AO, Almalki NK, Kamal NM (2020) Primary hyperoxaluria Type 1: a case report in an extended family with a novel AGXT gene mutation. Medicine 99:e20371. https://doi.org/10.1097/md.0000000000020371

    Article  PubMed  PubMed Central  Google Scholar 

  21. Mandrile G, Beck B, Acquaviva C, Rumsby G, Deesker L, Garrelfs S, Gupta A, Bacchetta J, Groothoff J, OxalEurope Consortium/Erknet Guideline Workgroup On Hyperoxaluria (2023) Genetic assessment in primary hyperoxaluria: why it matters. Pediatr Nephrol 38:625–634. https://doi.org/10.1007/s00467-022-05613-2

    Article  Google Scholar 

  22. Zhao F, Li J, Tang L, Li C, Wang W, Ning C (2021) Characteristics of the genotype and phenotype in Chinese primary hyperoxaluria type 1 populations. Urolithiasis 49:17–25. https://doi.org/10.1007/s00240-020-01201-x

    Article  CAS  PubMed  Google Scholar 

  23. Takayama T, Takaoka N, Nagata M, Johnin K, Okada Y, Tanaka S, Kawamura M, Inokuchi T, Ohse M, Kuhara T, Tanioka F, Yamada H, Sugimura H, Ozono S (2014) Ethnic differences in GRHPR mutations in patients with primary hyperoxaluria type 2. Clin Genet 86:342–348. https://doi.org/10.1111/cge.12292

    Article  CAS  PubMed  Google Scholar 

  24. Garrelfs SF, Rumsby G, Peters-Sengers H, Erger F, Groothoff JW, Beck BB, Oosterveld MJS, Pelle A, Neuhaus T, Adams B, Cochat P, Salido E, Lipkin GW, Hoppe B, Hulton SA; OxalEurope Consortium (2019) Patients with primary hyperoxaluria type 2 have significant morbidity and require careful follow-up. Kidney Int 96:1389–1399. https://doi.org/10.1016/j.kint.2019.08.018

    Article  CAS  Google Scholar 

  25. Eggermann T, Venghaus A, Zerres K (2012) Cystinuria: an inborn cause of urolithiasis. Orphanet J Rare Dis 7:19. https://doi.org/10.1186/1750-1172-7-19

    Article  PubMed  PubMed Central  Google Scholar 

  26. Mardi A, Heidary H, Mousavi SM, Khazaei G, Taghizadeh E (2021) A novel variant in iranian patient with cystinuria: a case report. Iran J Public Health 50:1897–1901. https://doi.org/10.18502/ijph.v50i9.7063

    Article  PubMed  PubMed Central  Google Scholar 

  27. Kim JH, Park E, Hyun HS, Lee BH, Kim GH, Lee JH, Park YS, Kang HG, Ha IS, Cheong HI (2017) Genotype and phenotype analysis in pediatric patients with cystinuria. J Korean Med Sci 32:310–314. https://doi.org/10.3346/jkms.2017.32.2.310

    Article  PubMed  Google Scholar 

  28. Chillaron J, Font-Llitjos M, Fort J, Zorzano A, Goldfarb DS, Nunes V, Palacin M (2010) Pathophysiology and treatment of cystinuria. Nat Rev Nephrol 6:424–434. https://doi.org/10.1038/nrneph.2010.69

    Article  CAS  PubMed  Google Scholar 

  29. Li C, Yang Y, Zheng Y, Shen F, Liu L, Li Y, Li L, Zhao Y (2020) Genetic and clinical analyses of 13 Chinese families with cystine urolithiasis and identification of 15 novel pathogenic variants in SLC3A1 and SLC7A9. Front Genet 11:74. https://doi.org/10.3389/fgene.2020.00074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Deejai N, Wisanuyotin S, Nettuwakul C, Khositseth S, Sawasdee N, Saetai K, Yenchitsomanus PT, Rungroj N (2019) Molecular diagnosis of solute carrier family 4 member 1 (SLC4A1) mutation-related autosomal recessive distal renal tubular acidosis. Lab Med 50:78–86. https://doi.org/10.1093/labmed/lmy051

    Article  PubMed  Google Scholar 

  31. Wang WJ, Xie JD, Yao H, Ding ZX, Jiang AR, Ma L, Shen HJ, Chen SN (2023) Identification of variants in 94 Chinese patients with hereditary spherocytosis by next-generation sequencing. Clin Genet 103:67–78. https://doi.org/10.1111/cge.14244

    Article  CAS  PubMed  Google Scholar 

  32. Guo W, Song Q, Zhang R, Xin Q, Liu Z, Lang Y, Zhao X, Shao L (2021) Genotypic and phenotypic analysis in 51 Chinese patients with primary distal renal tubular acidosis. Clin Genet 100:440–446. https://doi.org/10.1111/cge.14011

    Article  CAS  PubMed  Google Scholar 

  33. Runolfsdottir HL, Sayer JA, Indridason OS, Edvardsson VO, Jensson BO, Arnadottir GA, Gudjonsson SA, Fridriksdottir R, Katrinardottir H, Gudbjartsson D, Thorsteinsdottir U, Sulem P, Stefansson K, Palsson R (2021) Allele frequency of variants reported to cause adenine phosphoribosyltransferase deficiency. Eur J Hum Genet 29:1061–1070. https://doi.org/10.1038/s41431-020-00805-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Perdomo-Ramirez A, de Armas-Ortiz M, Ramos-Trujillo E, Suarez-Artiles L, Claverie-Martin F (2019) Exonic CLDN16 mutations associated with familial hypomagnesemia with hypercalciuria and nephrocalcinosis can induce deleterious mRNA alterations. BMC Med Genet 20:6. https://doi.org/10.1186/s12881-018-0713-7

    Article  PubMed  PubMed Central  Google Scholar 

  35. Mansour-Hendili L, Blanchard A, Le Pottier N, Roncelin I, Lourdel S, Treard C, González W, Vergara-Jaque A, Morin G, Colin E, Holder-Espinasse M, Bacchetta J, Baudouin V, Benoit S, Bérard E, Bourdat-Michel G, Bouchireb K, Burtey S, Cailliez M, Cardon G, Cartery C, Champion G, Chauveau D, Cochat P, Dahan K, De la Faille R, Debray FG, Dehoux L, Deschenes G, Desport E, Devuyst O, Dieguez S, Emma F, Fischbach M, Fouque D, Fourcade J, François H, Gilbert-Dussardier B, Hannedouche T, Houillier P, Izzedine H, Janner M, Karras A, Knebelmann B, Lavocat MP, Lemoine S, Leroy V, Loirat C, Macher MA, Martin-Coignard D, Morin D, Niaudet P, Nivet H, Nobili F, Novo R, Faivre L, Rigothier C, Roussey-Kesler G, Salomon R, Schleich A, Sellier-Leclerc AL, Soulami K, Tiple A, Ulinski T, Vanhille P, Van Regemorter N, Jeunemaître X, Vargas-Poussou R (2015) Mutation update of the CLCN5 gene responsible for dent disease 1. Hum Mutat 36:743–752. https://doi.org/10.1002/humu.22804

    Article  CAS  PubMed  Google Scholar 

  36. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17:405–424. https://doi.org/10.1038/gim.2015.30

  37. Moussa M, Papatsoris AG, Abou Chakra M, Moussa Y (2020) Update on cystine stones: current and future concepts in treatment. Intractable Rare Dis Res 9:71–78. https://doi.org/10.5582/irdr.2020.03006

    Article  PubMed  PubMed Central  Google Scholar 

  38. Singh P, Viehman JK, Mehta RA, Cogal AG, Hasadsri L, Oglesbee D, Olson JB, Seide BM, Sas DJ, Harris PC, Lieske JC, Milliner DS (2022) Clinical characterization of primary hyperoxaluria type 3 in comparison with types 1 and 2. Nephrol Dial Transplant 37:869–875. https://doi.org/10.1093/ndt/gfab027

    Article  CAS  PubMed  Google Scholar 

  39. Lin JA, Liao X, Wu W, Xiao L, Liu L, Qiu J (2021) Clinical analysis of 13 children with primary hyperoxaluria type 1. Urolithiasis 49:425–431. https://doi.org/10.1007/s00240-021-01249-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Lopez-Garcia SC, Emma F, Walsh SB, Fila M, Hooman N, Zaniew M, Bertholet-Thomas A, Colussi G, Burgmaier K, Levtchenko E, Sharma J, Singhal J, Soliman NA, Ariceta G, Basu B, Murer L, Tasic V, Tsygin A, Decramer S, Gil-Peña H, Koster-Kamphuis L, La Scola C, Gellermann J, Konrad M, Lilien M, Francisco T, Tramma D, Trnka P, Yüksel S, Caruso MR, Chromek M, Ekinci Z, Gambaro G, Kari JA, König J, Taroni F, Thumfart J, Trepiccione F, Winding L, Wühl E, Ağbaş A, Belkevich A, Vargas-Poussou R, Blanchard A, Conti G, Boyer O, Dursun I, Pınarbaşı AS, Melek E, Miglinas M, Novo R, Mallett A, Milosevic D, Szczepanska M, Wente S, Cheong HI, Sinha R, Gucev Z, Dufek S, Iancu D, Kleta R, Schaefer F, Bockenhauer D (2019) Treatment and long-term outcome in primary distal renal tubular acidosis. Nephrol Dial Transplant 34:981–991. https://doi.org/10.1093/ndt/gfy409

    Article  CAS  PubMed  Google Scholar 

  41. Alhasan KA, Shalaby MA, Albanna AS, Temsah MH, Alhayek Z, Abdalla MS, Alotaibi NG, Kalakattawi NM, Zaher ZF, Kari JA (2021) Comparison of renal stones and nephrocalcinosis in children: findings from two tertiary centers in Saudi Arabia. Front Pediatr 9:736308. https://doi.org/10.3389/fped.2021.736308

    Article  PubMed  Google Scholar 

  42. Prot-Bertoye C, Lebbah S, Daudon M, Tostivint I, Bataille P, Bridoux F, Brignon P, Choquenet C, Cochat P, Combe C, Conort P, Decramer S, Dore B, Dussol B, Essig M, Gaunez N, Joly D, Le Toquin-Bernard S, Mejean A, Meria P, Morin D, N’Guyen H V, Noel C, Normand M, Pietak M, Ronco P, Saussine C, Tsimaratos M, Friedlander G, Traxer O, Knebelmann B, Courbebaisse M; French Cystinuria Group (2015) CKD and its risk factors among patients with cystinuria. Clin J Am Soc Nephrol 10:842–851. https://doi.org/10.2215/CJN.06680714

    Article  Google Scholar 

Download references

Acknowledgements

We are very grateful to the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding (XMLX202101) for supporting this work.

Author information

Author notes

  1. Yukun Liu and Yucheng Ge contributed equally to this work.

Authors and Affiliations

  1. Department of Urology, Beijing Friendship Hospital, Capital Medical University, 95 YongAn Road, Xicheng District, Beijing, 100050, China

    Yukun Liu, Yucheng Ge, Ruichao Zhan, Zhenqiang Zhao, Jun Li & Wenying Wang

Authors
  1. Yukun Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yucheng Ge
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ruichao Zhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhenqiang Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wenying Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study’s conception and design. Study design and data collection: Yukun Liu, Yucheng Ge, and Wenying Wang. Data statistical analysis/interpretation: Ruichao Zhan and Zhenqiang Zhao. Yucheng Ge and Yukun Liu wrote the manuscript. Wenying Wang and Jun Li revised the manuscript. Ruichao Zhan and Zhenqiang Zhao prepared Figures and Tables. All authors reviewed the manuscript. All authors contributed to the revision and drafting of the article.

Corresponding author

Correspondence to Wenying Wang.

Ethics declarations

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Beijing Friendship Hospital, Capital Medical University (Date 02/01/2021/No. 2021-P2-019).

Consent to participate

Informed consent was obtained from the parents of the patients included in the study.

Conflicts of interest

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, Y., Ge, Y., Zhan, R. et al. Identification of mutations in 15 nephrolithiasis-related genes leading to a molecular diagnosis in 85 Chinese pediatric patients. Pediatr Nephrol 38, 3645–3661 (2023). https://doi.org/10.1007/s00467-023-06028-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-023-06028-3

Keywords

Search

Navigation