scholarly journals Mesenchymal stromal cell-based therapy in kidney diseases and transplantation

2019 ◽  
Vol 13 (1) ◽  
pp. 3-14
Author(s):  
Federica Casiraghi ◽  
Giuseppe Remuzzi

Intense investigation in pre-clinical models of kidney disease and transplantation showed that mesenchymal stromal cell (MSC) therapy acts on renal and inflammatory cells in multiple, complex and integrated ways, resulting in cell repair and regeneration, in the inhibition of inflammatory cells, and in the development of cells endowed with their own anti-inflammatory and immuneregulatory properties. These encouraging data paved the way for exploring the use of MSC in clinics as innovative therapeutic tools for patients with renal diseases and transplantation. In this review, we describe the available results of clinical studies of MSC in patients with post-cardiac surgery, acute kidney injury, chronic kidney diseases - including diabetes, renovascular disease and lupus nephritis - and in kidney transplant recipients, with a particular focus on our experience with MSC therapy as a pro-tolerogenic strategy in kidney transplantation. The available studies, mainly phase 1, indicated that MSC therapy is safe and feasible and not associated with adverse events, at least in the short- and mid-term. Encouraging results have been reported in renovascular disease and kidney transplantation, while studies in acute kidney injury and chronic kidney disease had contrasting outcomes. The relevant issues and the knowledge gap that still limit the translation of MSC cell therapy into clinical practice are discussed briefly.

2020 ◽  
Vol 245 (10) ◽  
pp. 902-910
Author(s):  
Binbin Pan ◽  
Guoping Fan

Kidney dysfunction, including chronic kidney disease and acute kidney injury, is a globally prevalent health problem. However, treatment regimens are still lacking, especially for conditions involving kidney fibrosis. Stem cells hold great promise in the treatment of chronic kidney disease and acute kidney injury, but success has been hampered by insufficient incorporation of the stem cells in the injured kidney. Thus, new approaches for the restoration of kidney function after acute or chronic injury have been explored. Recently, kidney organoids have emerged as a useful tool in the treatment of kidney diseases. In this review, we discuss the mechanisms and approaches of cell therapy in acute kidney injury and chronic kidney disease, including diabetic kidney disease and lupus nephritis. We also summarize the potential applications of kidney organoids in the treatment of kidney diseases. Impact statement Stem cells hold great promise in regenerative medicine. Pluripotent stem cells have been differentiated into kidney organoids to understand human kidney development and to dissect renal disease mechanisms. Meanwhile, recent studies have explored the treatment of kidney diseases using a variety of cells, including mesenchymal stem cells and renal derivatives. This mini-review discusses the diverse mechanisms underlying current renal disease treatment via stem cell therapy. We postulate that clinical applications of stem cell therapy for kidney diseases can be readily achieved in the near future.


Author(s):  
SHAREEF J. ◽  
SRIDHAR S. B. ◽  
SHARIFF A.

Proton pump inhibitors (PPIs) are most widely used medications for acid related gastrointestinal disorders. Accessible evidence based studies suggest that the increased use of PPI is linked to a greater risk of developing kidney diseases. This review aims to determine the association of kidney disease with the use of proton pump inhibitor with various study designs. PubMed, Scopus and Google Scholar databases as well as a reference list of relevant articles were systematically searched for studies by using the following search terms; ‘proton pump inhibitors’, ‘acute kidney injury’, ‘chronic kidney disease’ and ‘end stage renal disease’. Both observational and randomized controlled trials (RCTs) exploring the association of PPI use with kidney disease were eligible for inclusion. A total of 8 articles, including 9 studies (n = 794,349 participants) were identified and included in the review. Majority of the studies showed a higher risk of kidney outcomes in patients taking PPIs, with effect higher of acute kidney injury (4-to 6-fold) compared with chronic kidney disease and end stage renal disease (1.5-to 2.5-fold). However, the studies suggest that the strength of evidence is weak and could not prove causation. The risk increased considerably with the use of high dose of PPIs and prolonged duration of exposure necessitates the monitoring of renal function. Exercising vigilance in PPI use and cessation of proton pump inhibitor when there is no clear indication may be a reasonable approach to reduce the population burden of kidney diseases.


Cytotherapy ◽  
2019 ◽  
Vol 21 (5) ◽  
pp. e5
Author(s):  
R. Barcia ◽  
A. Allen ◽  
N. Vaninov ◽  
S. Nguyen ◽  
L. Goodale ◽  
...  

Stem Cells ◽  
2015 ◽  
Vol 33 (4) ◽  
pp. 1241-1253 ◽  
Author(s):  
Scott R. Burks ◽  
Ben A. Nguyen ◽  
Pamela A. Tebebi ◽  
Saejeong J. Kim ◽  
Michele N. Bresler ◽  
...  

2021 ◽  
pp. 1-17
Author(s):  
Hai Ning Wee ◽  
Jian-Jun Liu ◽  
Jianhong Ching ◽  
Jean-Paul Kovalik ◽  
Su Chi Lim

<b><i>Background:</i></b> The kynurenine pathway (KP) is the major catabolic pathway for tryptophan degradation. The KP plays an important role as the sole de novo nicotinamide adenine dinucleotide (NAD<sup>+</sup>) biosynthetic pathway in normal human physiology and functions as a counter-regulatory mechanism to mitigate immune responses during inflammation. Although the KP has been implicated in a variety of disorders including Huntington’s disease, seizures, cardiovascular disease, and osteoporosis, its role in renal diseases is seldom discussed. <b><i>Summary:</i></b> This review summarizes the roles of the KP and its metabolites in acute kidney injury (AKI) and chronic kidney disease (CKD) based on current literature evidence. Metabolomics studies demonstrated that the KP metabolites were significantly altered in patients and animal models with AKI or CKD. The diagnostic and prognostic values of the KP metabolites in AKI and CKD were highlighted in cross-sectional and longitudinal human observational studies. The biological impact of the KP on the pathophysiology of AKI and CKD has been studied in experimental models of different etiologies. In particular, the activation of the KP was found to confer protection in animal models of glomerulonephritis, and its immunomodulatory mechanism may involve the regulation of T cell subsets such as Th17 and regulatory T cells. Manipulation of the KP to increase NAD<sup>+</sup> production or diversion toward specific KP metabolites was also found to be beneficial in animal models of AKI. <b><i>Key Messages:</i></b> KP metabolites are reported to be dysregulated in human observational and animal experimental studies of AKI and CKD. In AKI, the magnitude and direction of changes in the KP depend on the etiology of the damage. In CKD, KP metabolites are altered with the onset and progression of CKD all the way to advanced stages of the disease, including uremia and its related vascular complications. The activation of the KP and diversion to specific sub-branches are currently being explored as therapeutic strategies in these diseases, especially with regards to the immunomodulatory effects of certain KP metabolites. Further elucidation of the KP may hold promise for the development of biomarkers and targeted therapies for these kidney diseases.


2016 ◽  
Vol 6 (1) ◽  
pp. 0-0
Author(s):  
K Kozłowska ◽  
J. Małyszko

Malignancy or its treatment affect kidney in several ways. The most common are acute kidney injury and chronic kidney disease. Other form of kidney diseases can also be present such as nephrotic syndrome, tubulointerstitial nephritis, thrombotic microangipathy etc. In addition, electrolyte abnormalities such as hypercalcemia, hyponatremia and hypernatremia, hypokalemia and hyperkalemia, and hypomagnesemia. are observed. Treatment of malignancy associated kidney disease is usually symptomatic. Cessation of the offending agent or other supportive measures if needed i.e. renal replacement therapy are also implemented.


Cytotherapy ◽  
2021 ◽  
Vol 23 (5) ◽  
pp. S20
Author(s):  
J. Teixiera ◽  
M.G. Atta ◽  
L. Noureddine ◽  
S. Nguyen ◽  
B. O’Rourke ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Lini Jin ◽  
Binfeng Yu ◽  
Ines Armando ◽  
Fei Han

The integrity and function of mitochondria are essential for normal kidney physiology. Mitochondrial DNA (mtDNA) has been widely a concern in recent years because its abnormalities may result in disruption of aerobic respiration, cellular dysfunction, and even cell death. Particularly, aberrant mtDNA copy number (mtDNA-CN) is associated with the development of acute kidney injury and chronic kidney disease, and urinary mtDNA-CN shows the potential to be a promising indicator for clinical diagnosis and evaluation of kidney function. Several lines of evidence suggest that mtDNA may also trigger innate immunity, leading to kidney inflammation and fibrosis. In mechanism, mtDNA can be released into the cytoplasm under cell stress and recognized by multiple DNA-sensing mechanisms, including Toll-like receptor 9 (TLR9), cytosolic cGAS-stimulator of interferon genes (STING) signaling, and inflammasome activation, which then mediate downstream inflammatory cascades. In this review, we summarize the characteristics of these mtDNA-sensing pathways mediating inflammatory responses and their role in the pathogenesis of acute kidney injury, nondiabetic chronic kidney disease, and diabetic kidney disease. In addition, we highlight targeting of mtDNA-mediated inflammatory pathways as a novel therapeutic target for these kidney diseases.


2016 ◽  
Vol 2016 ◽  
pp. 1-22 ◽  
Author(s):  
Anna Julie Peired ◽  
Alessandro Sisti ◽  
Paola Romagnani

Mesenchymal stem cells form a population of self-renewing, multipotent cells that can be isolated from several tissues. Multiple preclinical studies have demonstrated that the administration of exogenous MSC could prevent renal injury and could promote renal recovery through a series of complex mechanisms, in particular via immunomodulation of the immune system and release of paracrine factors and microvesicles. Due to their therapeutic potentials, MSC are being evaluated as a possible player in treatment of human kidney disease, and an increasing number of clinical trials to assess the safety, feasibility, and efficacy of MSC-based therapy in various kidney diseases have been proposed. In the present review, we will summarize the current knowledge on MSC infusion to treat acute kidney injury, chronic kidney disease, diabetic nephropathy, focal segmental glomerulosclerosis, systemic lupus erythematosus, and kidney transplantation. The data obtained from these clinical trials will provide further insight into safety, feasibility, and efficacy of MSC-based therapy in renal pathologies and allow the design of consensus protocol for clinical purpose.


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