Nephron. Experimental Nephrology

BACKGROUND: Lipoprotein abnormalities are associated with a rapid decline in renal function in patients of chronic kidney disease. In addition, hyperlipidemia is associated with an increased risk of developing renal insufficiency. The underlying molecular mechanisms for these clinical findings are unclear. We have previously reported a role for inhibitor of differentiation 3 (ID3), a transcription factor, in regulating kidney disease in hyperlipidemia. Introducing a genetic deficiency of Id3 in spontaneously hyperlipidemic apolipoprotein E knockout (Apoe(-/-)) mice led to accelerated mesangioproliferative glomerulonephritis...

BACKGROUND: In 2012, about 16,487 people received kidney transplants in the USA whereas 95,022 candidates were on the waiting list at the end of the year. Moreover, more than 2,600 kidneys procured annually for transplantation are discarded for a variety of reasons. We hypothesize that this pool of discarded kidneys could in part meet the growing, urgent need for transplantable kidneys using current methods for organ bioengineering and regeneration and surgical transplantation. The recellularization of extracellular matrix (ECM) scaffolds has the potential to meet the uniquely ambitious engineering challenges posed by complex solid organs such as the kidney...

BACKGROUND: Chronic kidney disease (CKD) is a global public health issue with an estimated prevalence of 8-16% worldwide. End-stage renal disease eventually develops every year in 0.15-0.2% of patients with overt CKD, and renal replacement therapy (RRT) with dialysis or transplantation is required. Although approximately 2 million people worldwide are currently on RRT to sustain life, this likely represents less than 10% of those who need it. The kidney transplant approach is also seriously impaired by limited graft survival and by the scarce availability of donors...

BACKGROUND: Chronic kidney disease affects 5-7% of people worldwide. The increasing number of patients and the shortage of transplantable organs create an imperative need to develop new methods for generating kidney tissue. SUMMARY: Recent advances in our understanding of the developmental biology of the kidney, along with the establishment of novel methodologies in the field of regenerative medicine, have created significant potential for kidney regeneration. These advances incorporate both transplantation of metanephric primordia into adult recipients and construction of 'fetal' kidney tissue from suspensions of single cells of metanephric origin...

BACKGROUND: With the rate of kidney disease on the rise, and a serious imbalance between the number of patients requiring a kidney transplant and the number of available donor kidneys, it is becoming increasingly important to develop alternative strategies to restore organ function to diminish the need for human donors. SUMMARY: We review the current progress and future directions of a subset of these strategies which are ultimately aimed towards bioengineering a functional, implantable, kidney-like tissue construct or organoid that might be genetically matched to the patient...

BACKGROUND: Millions of people are affected by irreversible loss of renal function and thus by a significantly increased cardiovascular risk. In this context, the parietal epithelial cells (PECs) of the glomerulus have attracted increasing attention in recent years. So far, they have been ascribed 2 major functions: (1) PECs may act as intrinsic progenitor cells to replenish podocytes and/or proximal tubular cells and (2) a major role of PECs has been proposed in 2 glomerular disease entities [i...

BACKGROUND: The incidence of kidney diseases is increasing worldwide and they are emerging as a major public health problem. Once mostly considered inexorable, renal disease progression can now be halted and lesions can even regress with drugs such as angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II type I receptor blockers, indicating the possibility of kidney repair. SUMMARY: The discovery of renal progenitor cells lining the Bowman capsule of adult rat and human kidneys has shed light on the mechanism of repair by ACEi...

BACKGROUND: Various cell types, including podocytes and parietal epithelial cells, play important roles in the development and progression of glomerular kidney diseases, albuminuria, and glomerulosclerosis. Besides their role in renal pathologies, glomerular cells have emerging new functions in endogenous repair mechanisms. A better understanding of the dynamics of the glomerular environment and cellular composition in an intact living kidney is critically important for the development of new regenerative therapeutic strategies for kidney diseases...

BACKGROUND: Based upon observations which indicate that chronic intrarenal hypoxia and microvascular obliteration play an important role in the pathogenesis of renal scarring and loss of function, the idea is presented that restoration of kidney structure and function by arresting microvascular drop-out and restoring the interstitial capillary network could be a feasible approach to regeneration of a diseased kidney. This paper addresses the reasoning behind this possibility. SUMMARY: A 'unifying vasculogenic hypothesis' is discussed which proposes that, in hypoxic nephrons which retain poorly functioning vascular and epithelial elements, the disease process can be slowed or arrested, and nephrons regenerated, by adoptive transfer of endothelial progenitor cells to restore interstitial and glomerular vascular integrity...

BACKGROUND: The most common intrarenal cause for acute kidney injury/renal failure is tubular damage. The kidney tubules are arranged as compartments of cellular mosaics to perform their functions, and at rest almost a fifth of the human ATP consumption is allotted to the reabsorption of substances from the filtrate, rendering especially the proximal tubules highly sensitive to oxygen and/or nutrient deprivation. Normally mitotically quiescent, the tubular epithelium shows a brisk regenerative response following injury if supportive care is offered, allowing functional restoration...

BACKGROUND: For many years, the glomerulus was considered incapable of regeneration. However, experimental and clinical evidence challenged this concept and showed that glomerular injury and even glomerulosclerosis can undergo regression under certain circumstances. The problem with glomerular regeneration is centered around the podocyte, a highly specialized cell that is the critical constituent of the glomerular filtration barrier. SUMMARY: Podocytes are characterized by a complex cytoskeleton that makes them unable to proliferate...

BACKGROUND: Since no specific or radical treatments have yet been established for acute kidney injury (AKI), the development of cell transplantation therapy using renal progenitors is desirable as a new therapeutic option for AKI. The recent advances in developmental biology, stem cell biology, and nephrology have led to an increased availability of renal progenitors from multiple sources. SUMMARY: Four main sources of renal progenitors have been described so far: isolation from (1) embryonic or (2) adult kidneys, (3) directed differentiation of pluripotent stem cells such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), and (4) cellular reprogramming of fully differentiated adult renal cells...

BACKGROUND: Acute kidney injury (AKI) is emerging as a public health problem in developing and developed countries. It affects up to 7% of hospitalized patients, with a higher prevalence in critical care units. Despite major advances in preventive strategies and support measures, the mortality rate among patients remains higher than 50%. Several pharmacological approaches to improve renal function and survival after an AKI episode have been largely unsuccessful in clinical practice. SUMMARY: Stem cell-based therapy has provided new hopes of innovative interventions to enhance the limited capability of kidney regeneration in AKI...

BACKGROUND: Kidney regeneration is currently gaining considerable attention in place of kidney dialysis as the ultimate therapeutic strategy for renal failure. However, because of anatomical complications, the kidney is believed to be the hardest organ to regenerate. Such a complicated organ is virtually impossible to imagine being completely rebuilt de novo from stem cells. Nevertheless, several research groups are attempting this large challenge. SUMMARY: There are 4 major strategies for de novo kidney regeneration from stem cells...

BACKGROUND: Several organs such as the skin and liver have a great capacity for regeneration. However, many approaches only delay the progression of end-stage kidney disease and do not achieve efficient long-term stabilization, let alone regeneration. SUMMARY: In mammals, the kidney has an innate but limited capacity for regeneration which can only modify the nephron structure and function but not increase the nephron number. Several clinical and animal studies have indicated that functional improvements and/or structural regression can occur in chronic kidney disease...

BACKGROUND: Chronic and acute kidney injury damages nephrons, the blood filtering tubules in the kidney. Although mammalian kidneys can regenerate the tubular epithelium of the nephron, no new nephrons are made during adulthood. In contrast, fish are capable of growing nephrons de novo throughout their life. A better understanding of this 'neo-nephrogenic' response in fish may lead to the development of novel regenerative therapies to treat kidney disease in humans. SUMMARY: In this review, nephron formation in the fish mesonephric kidney during normal growth and in response to acute injury is examined at the morphological and molecular levels...

BACKGROUND: Kidney diseases are worldwide public health problems with a high cost and increasing incidence. By revealing the genetic and cellular mechanism behind mammalian kidney development, better diagnostic methods and novel therapies can be expected to be developed. The mammalian kidney is a typical organ that develops on the basis of sequential and reciprocal cell and tissue interactions. Functional genetic analysis has identified that genes from different classes are involved in the construction of the kidney and the same genes are also connected to the development of diseases...

BACKGROUND: Plants are characterized by indeterminate post-embryonic development that is evident, for example, in the continuous branching of shoots and roots. High competence to regenerate tissues is another consequence of such intrinsic developmental plasticity in plants. It has been suggested that specialized groups of cells within plant meristems should be compared to stem cells in animals, but the utility of this label in the context of post-embryonic plant development and regeneration is often debated...

No abstract text is available yet for this article.

BACKGROUND: Recent studies have suggested that aldosterone (Aldo) plays a key role in the pathogenesis of renal injury; however, the molecular mechanisms of Aldo-induced renal injury have not been characterized. This study was performed to test the hypothesis that reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress contribute to the pathogenesis of Aldo- and salt-induced renal injury. METHODS: Rats were uninephrectomized and treated with one of the following for 4 weeks: (1) vehicle, (2) vehicle + NaCl, (3) Aldo + NaCl or (4) Aldo + NaCl + N-acetyl-L-cysteine (NAC)...