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The following is a summary of “Personalized disease recurrence modeling using iPSC-derived podocytes in patients with idiopathic nephrotic syndrome,” published in the February 2025 issue of Nephrology Dialysis Transplantation by Berge et al. 

Primary focal segmental glomerulosclerosis (FSGS) causes podocyte injury and treatment-resistant nephrotic syndrome. Recurrence of the original disease after kidney transplantation (rFSGS) affects 10-50% of transplant patients, likely due to unidentified circulating permeability factors (CPF). 

Researchers conducted a retrospective study to assess donor podocyte susceptibility to CPF in (r)FSGS. They developed a personalized model using induced pluripotent stem cell (iPSC)-derived podocytes from patients and kidney donors. 

They included five patients and their living kidney donors: three with rFSGS, two without symptoms, and one (P5) with NPHS2 heterozygous mutations. Peripheral blood mononuclear cells were reprogrammed into iPSC and differentiated into podocytes. iPSC-derived podocytes were exposed to CPF-containing plasma/serum from corresponding patients. Podocyte injury was assessed using ROS formation, cellular granularity induction, and quantitative F-actin redistribution (FAR) assessment. Crossmatch experiments evaluated donor podocyte susceptibility to CPF-induced injury. 

The results showed successful podocyte differentiation by morphology and protein expression. Only FAR consistently differentiated patient and donor samples. All pre-transplant patient samples except P5 caused significant FAR in patient podocytes. Donor podocytes showed significant FAR with corresponding patient samples in rFSGS but not in non-rFSGS cases. Effects on non-corresponding donor podocytes varied. 

Investigators found that in vitro assays using iPSC-derived donor podocytes allowed individualized assessment of rFSGS. Larger cohort studies were required to validate the findings. 

Source: academic.oup.com/ndt/advance-article/doi/10.1093/ndt/gfaf045/8046456