OPINION

Precision Nephrology: Understanding Kidney Injury To Bring The Right Drug To The Right Person

FIGURE 1  |  Patient iPSC-derived kidney organoid captures an individual’s unique genetic identity. The figure outlines how the technology could be applied specifically to APOL1-nephropathy.

Patient iPSC-derived kidney organoid captures an  individual's unique genetic identity.

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.

Meet The Experts

 

RAVI I. THADHANI, MD, MPH
Chief Academic Officer, Mass General Brigham

OPEYEMI A. OLABISI, MD, PhD
Assistant Professor of Medicine, Duke Department of Medicine, Division of Nephrology

References

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  11. Genovese G, Friedman DJ, Ross MD, et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 2010 Aug 13;329(5993):841-5. doi: 10.1126/science.1193032. 
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