Advances in Diagnosis and Treatment of Inherited Kidney Diseases in Children

Overview

Journal Kidney Dis (Basel)

Specialty Nephrology

Date 2024 Dec 12

PMID 39664340

Authors

Guozhen Wang

Mengqiu Liao

Danny Junyi Tan

Xiangjun Chen

Ran Chao

Yifan Zhu

Pan Li

Yuelin Guan

Jianhua Mao

Lidan Hu

Affiliations

Soon will be listed here.

Abstract

Background: Inherited kidney diseases (IKDs) in children pose unique diagnostic and therapeutic challenges. IKD significantly impact patient quality of life, morbidity, mortality, and cost to the healthcare system. With over 150 genetic abnormalities, they account for approximately 30% of cases requiring renal replacement therapy. There is an urgent need to advance both diagnosis and treatment strategies. In this review, we present recent advances in diagnosis and treatment for facilitating personalized treatment approaches.

Summary: The diagnostic landscape for IKDs have evolved significantly, emphasizing precise genetic identification and classification of these disorders. Recent advancements include the refinement of genetic testing techniques, such as whole exome sequencing, which has improved the accuracy of diagnosing specific diseases and facilitated early intervention strategies. Additionally, this review categorizes IKDs based on genetic abnormalities and clinical manifestations, enhancing understanding and management approaches. Finally, it summarizes the corresponding treatment, and lists the application of emerging therapeutic options such as gene therapy and organoids, which show promise in transforming treatment outcomes.

Key Messages: This review summarizes the common types of IKDs in children, including their diagnosis and treatment advances, and provides an update on the status of gene therapy development for these disorders.

References

Liu J, Sadeh T, Lippiat J, Thakker R, Black G, Manson F . Small molecules restore the function of mutant CLC5 associated with Dent disease. J Cell Mol Med. 2020; 25(2):1319-1322. PMC: 7812281. DOI: 10.1111/jcmm.16091. View

Devlin L, Dhondurao Sudhindar P, Sayer J . Renal ciliopathies: promising drug targets and prospects for clinical trials. Expert Opin Ther Targets. 2023; 27(4-5):325-346. DOI: 10.1080/14728222.2023.2218616. View

Murray S, Fennelly N, Doyle B, Lynch S, Conlon P . Integration of genetic and histopathology data in interpretation of kidney disease. Nephrol Dial Transplant. 2020; 35(7):1113-1132. DOI: 10.1093/ndt/gfaa176. View

Nesterova G, Gahl W . Cystinosis: the evolution of a treatable disease. Pediatr Nephrol. 2012; 28(1):51-9. PMC: 3505515. DOI: 10.1007/s00467-012-2242-5. View

Forsythe E, Kenny J, Bacchelli C, Beales P . Managing Bardet-Biedl Syndrome-Now and in the Future. Front Pediatr. 2018; 6:23. PMC: 5816783. DOI: 10.3389/fped.2018.00023. View

Miao M, Feng L, Wang J, Xu C, Su X, Zhang G . A novel splicing variant identified in a fetus with autosomal recessive polycystic kidney disease. Front Genet. 2023; 14:1207772. PMC: 10339289. DOI: 10.3389/fgene.2023.1207772. View

Guay-Woodford L, Bissler J, Braun M, Bockenhauer D, Cadnapaphornchai M, Dell K . Consensus expert recommendations for the diagnosis and management of autosomal recessive polycystic kidney disease: report of an international conference. J Pediatr. 2014; 165(3):611-7. PMC: 4723266. DOI: 10.1016/j.jpeds.2014.06.015. View

Vivante A, Hildebrandt F . Exploring the genetic basis of early-onset chronic kidney disease. Nat Rev Nephrol. 2016; 12(3):133-46. PMC: 5202482. DOI: 10.1038/nrneph.2015.205. View

Madhivanan K, Ramadesikan S, Hsieh W, Aguilar M, Hanna C, Bacallao R . Lowe syndrome patient cells display mTOR- and RhoGTPase-dependent phenotypes alleviated by rapamycin and statins. Hum Mol Genet. 2020; 29(10):1700-1715. PMC: 7322567. DOI: 10.1093/hmg/ddaa086. View

10.

Li Y, Fan J, Zhu W, Niu Y, Wu M, Zhang A . Therapeutic Potential Targeting Podocyte Mitochondrial Dysfunction in Focal Segmental Glomerulosclerosis. Kidney Dis (Basel). 2023; 9(4):254-264. PMC: 10601935. DOI: 10.1159/000530344. View

11.

Tavira B, Gomez J, Santos F, Gil H, Alvarez V, Coto E . A labor- and cost-effective non-optical semiconductor (Ion Torrent) next-generation sequencing of the SLC12A3 and CLCNKA/B genes in Gitelman's syndrome patients. J Hum Genet. 2014; 59(7):376-80. DOI: 10.1038/jhg.2014.37. View

12.

Elmonem M, Veys K, Soliman N, Van Dyck M, Van den Heuvel L, Levtchenko E . Cystinosis: a review. Orphanet J Rare Dis. 2016; 11:47. PMC: 4841061. DOI: 10.1186/s13023-016-0426-y. View

13.

Li H, Wang C, Che R, Zheng B, Zhou W, Huang S . A Potential Therapy Using Antisense Oligonucleotides to Treat Autosomal Recessive Polycystic Kidney Disease. J Clin Med. 2023; 12(4). PMC: 9966971. DOI: 10.3390/jcm12041428. View

14.

Harambat J, van Stralen K, Espinosa L, Groothoff J, Hulton S, Cerkauskiene R . Characteristics and outcomes of children with primary oxalosis requiring renal replacement therapy. Clin J Am Soc Nephrol. 2012; 7(3):458-65. PMC: 3302673. DOI: 10.2215/CJN.07430711. View

15.

Zeng M, Di H, Liang J, Liu Z . Effectiveness of renin-angiotensin-aldosterone system blockers in patients with Alport syndrome: a systematic review and meta-analysis. Nephrol Dial Transplant. 2023; 38(11):2485-2493. DOI: 10.1093/ndt/gfad105. View

16.

Alanazi R, Alhwity B, Almahlawi R, Alatawi B, Albalawi S, Albalawi R . Multilineage Differentiating Stress Enduring (Muse) Cells: A New Era of Stem Cell-Based Therapy. Cells. 2023; 12(13). PMC: 10340735. DOI: 10.3390/cells12131676. View

17.

Gabriel S, Belge H, Gassama A, Debaix H, Luciani A, Fehr T . Bone marrow transplantation improves proximal tubule dysfunction in a mouse model of Dent disease. Kidney Int. 2017; 91(4):842-855. DOI: 10.1016/j.kint.2016.11.016. View

18.

Shi B, Ying T, Chadban S . Survival after kidney transplantation compared with ongoing dialysis for people over 70 years of age: A matched-pair analysis. Am J Transplant. 2023; 23(10):1551-1560. DOI: 10.1016/j.ajt.2023.07.006. View

19.

Shah V, Pyle L . Lumasiran, an RNAi Therapeutic for Primary Hyperoxaluria Type 1. N Engl J Med. 2021; 385(20):e69. DOI: 10.1056/NEJMc2107661. View

20.

Cornec-Le Gall E, Audrezet M, Le Meur Y, Chen J, Ferec C . Genetics and pathogenesis of autosomal dominant polycystic kidney disease: 20 years on. Hum Mutat. 2014; 35(12):1393-406. DOI: 10.1002/humu.22708. View