Precision Nephrology: Understanding Kidney Injury to Bring the Right Drug to the Right Person
Another kidney disease that is likely to benefit early from human kidney organoid models is polycystic kidney disease (PKD). Kidney organoids from individuals with PKD develop large cysts that mimic kidney cysts seen in people with PKD, indicating that such organoids may be the ideal tool for drug discovery.13,14
Precision medicine, however, did not yield SGLT-2i, which has dramatically improved CKD management. Therefore, why advocate for this cumbersome, costly approach? Because unlike in oncology, where precision medicine frequently guides drug discovery, the success rate of drug discovery in nephrology is abysmal. There has been over a 30-year gap between the approval of ACE inhibitors and recent approval of SGLT-2i for slowing CKD progression. At this rate, the next breakthrough kidney drug will be approved in 2050, after three million new people will have reached dialysis in the US alone.
Patient-derived kidney organoids may help accelerate the discovery of therapeutic targets and more efficiently identify potential toxicities of candidate drugs. Nephrology writ large is being transformed by a deeper understanding of biology, genetics, and novel technologies, all poised to set the stage for improving the understanding and treatment of kidney injury.
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- He B, Chen P, Zambrano S, et al. Single-cell RNA sequencing reveals the mesangial identity and species diversity of glomerular cell transcriptomes. Nat Commun 2021 Apr 9;12(1):2141. doi: 10.1038/s41467-021-22331-9.
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- Larsen CP, Beggs ML, Saeed M, Walker PD. Apolipoprotein L1 risk variants associate with systemic lupus erythematosus-associated collapsing glomerulopathy. J Am Soc Nephrol 2013 Apr;24(5):722-5. doi: 10.1681/ASN.2012121180.
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- Wu H, Larsen CP, Hernandez-Arroyo CF, et al. AKI and collapsing glomerulopathy associated with COVID-19 and APOL 1 high-risk genotype. J Am Soc Nephrol 2020 Aug;31(8):1688-95. doi: 10.1681/ASN.2020050558.
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- Kuraoka S, Tanigawa S, Taguchi A, et al. PKD1-dependent renal cystogenesis in human induced pluripotent stem cell-derived ureteric bud/collecting duct organoids. J Am Soc Nephrol 2020 Oct;31(10):2355-71. doi: 10.1681/ASN.2020030378.