Kidney disease causes significant suffering and premature death worldwide. Because there is no cure for kidney failure and limited treatment options, there is an urgent need to develop effective pharmacological interventions to slow or prevent the progression of kidney disease.

In the review, Kirsty M. Rooney, Adrian S. Woolf, and Susan J. Kimber consider the feasibility of using human pluripotent stem cell-derived renal tissue or organoids to model inherited renal diseases. Significant success has been achieved in modeling inherited renal tubular diseases (e.g., cystinosis), polycystic kidney disease, and medullary cystic kidney disease. Organoid models have also been used to test new therapies that improve abnormal cell biology. Despite the immaturity of glomeruli development in organoids, some progress has been made in modeling congenital glomerular diseases. Less progress has been made in modeling structural renal malformations, likely because fully mature posterior renal mesenchymal-derived renal units, ureteral bud-derived branching collecting ducts and significant stromal cell populations cannot be generated simultaneously in a single scenario. Key message: they predict significant progress in this field if organoids can generate complete cell lines and if renal components display key physiological functions (e.g., glomerular filtration). Future economic scale escalation of replicable organoid generation will facilitate broader research applications, including potential therapeutic applications of these stem cell-based technologies.

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End-stage renal disease (ESRD) affects millions of people worldwide. Since dialysis and transplantation are expensive, life-saving treatments that are not available in every country, there is an urgent need to find new ways to treat primary kidney disease. Until a few years ago, researchers have been limited to studying the following: cell lines (mesangial, tubular, and podocytes) grown from native human kidneys; mutant mice; and experimental animals exposed to injuries such as nephrotoxins, altered diet, renal ischemia, or urinary flow obstruction. While these studies have provided considerable insight, another strategy is to create diseased human kidneys in the laboratory. These models can then be used to study the pathobiology and as a test bed for identifying new therapies.

Human pluripotent stem cell (hPSC) technology offers an option to achieve this ideal, and we review here the extent to which so-called "kidney organs," i.e., developing kidney-like tissues derived from hPSCs, can mimic certain inherited kidney diseases. hPSCs have the ability to self-replicate indefinitely and can also differentiate into the 3 major tissue layers found in the embryo (mesoderm, endoderm, and ectoderm) and then differentiate into specific cell types found in the mature organism. Two major sources of hematopoietic stem cells have emerged: embryonic stem cells (ESCs) and, more recently, induced pluripotent stem cells (iPSCs). Human ESCs are obtained from early human embryos produced by in vitro fertilization: these embryos are usually redundant and are not used to initiate pregnancy. hiPSCs are made by reprogramming adult cells, for example, cells harvested from blood samples or skin biopsies.

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Etiology of congenital kidney diseases

Malformations of the renal tract (i.e., kidney and/or urethra) account for approximately one-third of all congenital birth defects. In addition, about half of the children and a quarter of young adults with ESRD are born with abnormal kidney structures. The most severe malformation is renal agenesis, in which the kidney is not formed during the embryonic period. The next most severe is renal hypoplasia, in which the kidney begins to form but contains immature and metaplastic tissue. The mildest anatomical defect is renal hypoplasia, where the organ contains fewer glomeruli than normal, which predisposes the individual to hypertension and impaired renal function later in life.

In other young children with ESRD, the kidneys appear anatomically intact, but terminal differentiation of specific cell types is failing. Examples include congenital nephrotic syndrome, in which podocytes fail to mature, and early-onset tubulopathy, in which terminal differentiation of the renal tubules or collecting ducts is incomplete.

It is known that some of these disorders are caused by mutations in specific genes expressed during normal kidney development and differentiation. Although it is possible that all individuals born with abnormal kidneys will be found to have mutations, studies of patient populations have detected convincing pathogenic gene variants in only a minority of individuals. Experimental studies in human epidemiology and rodents have shown that a range of environmental disturbances can interfere with kidney development, including alterations in maternal diet, placental insufficiency leading to hypoxia, and teratogenic agents such as retinoids and angiotensin inhibitors. Whether these deleterious effects are mediated through direct toxicity or more subtle mechanisms (e.g., affecting epigenetic regulation) remains to be determined.

up to now, human kidney organoid technology has not been used to model environmental perturbations, which would be an interesting direction for future research.

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Treatment of congenital kidney disease

In some cases, no treatment is required. The small problem of urination through the ureter and urethra disappears when the child grows up. Even if one of the kidneys is missing or damaged, treatment is not needed. Even with only partial kidney function or one kidney, you can live a healthy life. Cistanche tubulosa extract is used in daily life to help improve kidney function. Phenylethanoid glycosides, Verbascoside, and Echinacoside in Cistanche tubulosa can increase the value-added rate of kidney cells up to 8-10 times and inhibit apoptosis as well as improve the repair of damaged kidney cells.

In other cases, treatment ranging from medication to surgery may be needed to maintain health.

1. When vesicoureteral reflux is found, treatment may include:

Antibiotics to prevent urinary tract infections, where urine pressure flows that might otherwise spread to the kidneys and blood to reconnect the ureter to the bladder, surgery to create an opening that closes when the bladder is full, or other procedures to help prevent reflux

2. In cases of severe ureteral or urethral blockage, treatment may include:

Surgery to clear the blockage, when congenital anomalies of the kidney and urinary tract are not detected early enough, or in cases where treatment cannot prevent serious damage to the kidney

3. Kidney failure may require the following treatments: Dialysis and kidney transplantation

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