TABLE 2.

The main outcomes, limitations and future perspectives of the hiPSCs-derived organoids models of kidney diseases are described.

Kidney organoid models of disease
Model-disease type and references	Outcomes	Limitations and challenges	Future perspectives
Mucin 1 kidney disease (MKD) Dvela-Levitt et al., 2019	Human iPSC-derived organoids from MKD patients exhibited Muc1 protein mislocalization in tubular cells. Organoid cells responded to the drug BRD90 in a similar manner as in mouse models and patients with MKD.	No functional assays, such as tubular absorption, were carried out in MKD organoids.	Developing semi-automated culture systems and analysis approaches can make this system a valuable drug testing tool for MKD.
Polycystic kidney disease (PKD) Freedman et al., 2015; Cruz et al., 2017; Czerniecki et al., 2018; Low et al., 2019	These human organoids from PKD1/PKD2 KO hiPSCs extensively formed cysts in vitro and can be adapted to high-throughput screening. Using this culture format, a potential involvement of non-muscle myosin in cystogenesis was identified.	PKD patient-derived hiPSCs did not sufficiently form cysts, hampering the application of this organoid system to study the genotypes of patients.	Optimizing culture conditions to induce cysts in patient-derived organoids will provide a highly useful assay for studying disease pathogenesis and developing personalized therapeutic strategies.
ITF40 Nephronophthisis ciliopathic renal disease Forbes et al., 2018	Somatic cells from a patient with compound heterozygous mutations in IFT140 were reprogrammed and corrected with CRISPR/Cas9. Primary cilia and apico-basal defects were observed in tubular cells of patient-derived kidney organoids but not in gene-corrected isogenic controls.	Primary cilia and spheroid polarity defects were not present in all organoids, which limits the potential use of the system in drug screening applications.	Generation of iPSC-derived organoids from patients with different mutations in NPHP genes will help to elucidate the mechanisms of Nephronophthisis pathogenesis and explain the differences between the clinical phenotypes.
Podocalyxin deficiency Kim et al., 2017	Knockout of podocalyxin demonstrated its importance for microvilli formation and podocyte spacing. Podocalyxin-KO organoids phenocopied, to some degree, the pathological features of the kidney in podocalyxin knockout mice, validating the use of organoids for understanding human podocyte development.	Podocalyxin deficiency is not compatible with life, and newborns with such defects are rarely reported. Therefore, although podocalyxin-deficient organoids can be used to study the role of podocalyxin in early steps of organogenesis, are less useful for studies in adult human diseases.	A mutation variant of unknown significance in PODXL has been identified in humans, the generation of patient-specific hiPSCs and their differentiation could be a valuable tool to investigate the pathogenesis of PODXL mutations in humans.