Kidney Failure Stem Cell Treatment

Kidney Failure Stem Cell Therapy

Stem Cell Treatments for Kidney Failure are now available at SIRM

Renal failure or kidney failure (formerly called renal insufficiency) describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood. Two forms:

  • acute (acute kidney injury)
  • chronic (chronic kidney disease)
  • a number of other diseases or health problems may cause either form of renal failure to occur.

Renal failure is described as a decrease in glomerular filtration rate. Biochemically, renal failure is typically detected by an elevated serum creatinine level.

Problems frequently encountered in kidney malfunction include abnormal fluid levels in the body, deranged acid levels, abnormal levels of potassium, calcium, phosphate, and (in the longer term) anemia as well as delayed healing in broken bones. Depending on the cause, hematuria (blood loss in the urine) and proteinuria (protein loss in the urine) may occur. Long-term kidney problems have significant repercussions on other diseases, such as cardiovascular disease.Kidney Failure Stem Cell Treatment

 

 

 

 

 

 

 

Stem Cell Treatments for Kidney Failure at SIRM

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Related Articles Light Chain Proximal Tubulopathy: Clinical and Pathologic Characteristics in the Modern Treatment Era. J Am Soc Nephrol. 2016 May;27(5):1555-65 Authors: Stokes MB, Valeri AM, Herlitz L, Khan AM, Siegel DS, Markowitz GS, D'Agati VD Abstract Light chain proximal tubulopathy (LCPT) is characterized by cytoplasmic inclusions of monoclonal LC within proximal tubular cells. The significance of crystalline versus noncrystalline LCPT and the effect of modern therapies are unknown. We reported the clinical-pathologic features of 40 crystalline and six noncrystalline LCPT patients diagnosed between 2000 and 2014. All crystalline LCPTs were κ-restricted and displayed acute tubular injury. One-third of noncrystalline LCPT patients displayed λ-restriction or acute tubular injury. Only crystalline LCPT frequently required antigen retrieval to demonstrate monoclonal LC by immunofluorescence. In five of 38 patients, crystals were not detectable by light microscopy, but they were visible by electron microscopy. Hematolymphoid neoplasms, known before biopsy in only 15% of patients, included 21 monoclonal gammopathies of renal significance; 15 multiple myelomas; seven smoldering multiple myelomas; and three other neoplasms. Biopsy indications included Fanconi syndrome (38%; all with crystalline LCPT), renal insufficiency (83%), and proteinuria (98%). Follow-up was available for 30 (75%) patients with crystalline LCPT and all six patients with noncrystalline LCPT, of whom 11 underwent stem cell transplant, 16 received chemotherapy only, and nine were untreated. Complete or very good partial hematologic remissions occurred in six of 22 treated crystalline LCPT patients. By multivariable analysis, the only independent predictor of final eGFR was initial eGFR, highlighting the importance of early detection. All patients with crystalline LCPT treated with stem cell transplant had stable or improved kidney function, indicating the effectiveness of aggressive therapy in selected patients. PMID: 26374607 [PubMed - indexed for MEDLINE]
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Related Articles Human Induced Pluripotent Stem Cell-Derived Podocytes Mature into Vascularized Glomeruli upon Experimental Transplantation. J Am Soc Nephrol. 2016 Jun;27(6):1778-91 Authors: Sharmin S, Taguchi A, Kaku Y, Yoshimura Y, Ohmori T, Sakuma T, Mukoyama M, Yamamoto T, Kurihara H, Nishinakamura R Abstract Glomerular podocytes express proteins, such as nephrin, that constitute the slit diaphragm, thereby contributing to the filtration process in the kidney. Glomerular development has been analyzed mainly in mice, whereas analysis of human kidney development has been minimal because of limited access to embryonic kidneys. We previously reported the induction of three-dimensional primordial glomeruli from human induced pluripotent stem (iPS) cells. Here, using transcription activator-like effector nuclease-mediated homologous recombination, we generated human iPS cell lines that express green fluorescent protein (GFP) in the NPHS1 locus, which encodes nephrin, and we show that GFP expression facilitated accurate visualization of nephrin-positive podocyte formation in vitro These induced human podocytes exhibited apicobasal polarity, with nephrin proteins accumulated close to the basal domain, and possessed primary processes that were connected with slit diaphragm-like structures. Microarray analysis of sorted iPS cell-derived podocytes identified well conserved marker gene expression previously shown in mouse and human podocytes in vivo Furthermore, we developed a novel transplantation method using spacers that release the tension of host kidney capsules, thereby allowing the effective formation of glomeruli from human iPS cell-derived nephron progenitors. The human glomeruli were vascularized with the host mouse endothelial cells, and iPS cell-derived podocytes with numerous cell processes accumulated around the fenestrated endothelial cells. Therefore, the podocytes generated from iPS cells retain the podocyte-specific molecular and structural features, which will be useful for dissecting human glomerular development and diseases. PMID: 26586691 [PubMed - indexed for MEDLINE]
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Related Articles IGF-1 C Domain-Modified Hydrogel Enhances Cell Therapy for AKI. J Am Soc Nephrol. 2016 Aug;27(8):2357-69 Authors: Feng G, Zhang J, Li Y, Nie Y, Zhu D, Wang R, Liu J, Gao J, Liu N, He N, Du W, Tao H, Che Y, Xu Y, Kong D, Zhao Q, Li Z Abstract Low cell retention and engraftment after transplantation limit the successful application of stem cell therapy for AKI. Engineered microenvironments consisting of a hydrogel matrix and growth factors have been increasingly successful in controlling stem cell fate by mimicking native stem cell niche components. Here, we synthesized a bioactive hydrogel by immobilizing the C domain peptide of IGF-1 (IGF-1C) on chitosan, and we hypothesized that this hydrogel could provide a favorable niche for adipose-derived mesenchymal stem cells (ADSCs) and thereby enhance cell survival in an AKI model. In vitro studies demonstrated that compared with no hydrogel or chitosan hydrogel only, the chitosan-IGF-1C hydrogel increased cell viability through paracrine effects. In vivo, cotransplantation of the chitosan-IGF-1C hydrogel and ADSCs in ischemic kidneys ameliorated renal function, likely by the observed promotion of stem cell survival and angiogenesis, as visualized by bioluminescence imaging and attenuation of fibrosis. In conclusion, IGF-1C immobilized on a chitosan hydrogel provides an artificial microenvironment for ADSCs and may be a promising therapeutic approach for AKI. PMID: 26869006 [PubMed - indexed for MEDLINE]
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Related Articles Echocardiography-Defined Pulmonary Hypertension in Multiple Myeloma: Risk Factors and Impact on Outcomes. South Med J. 2016 May;109(5):282-9 Authors: Sangani RG, Butler M, Kirchner HL, Berger A, Stamm JA Abstract OBJECTIVES: Survival of patients with multiple myeloma (MM) has improved as a result of therapeutic advances. There is evidence that some patients with MM develop pulmonary hypertension (PH). The objective of this study was to identify risk factors of echocardiographic PH and its impact on outcomes of patients with MM. METHODS: We conducted a retrospective study of patients with MM (N = 359) diagnosed between 2000 and 2011 within the Geisinger Medical Center. Chart review was conducted on the subgroup of patients who underwent a transthoracic echocardiogram within 2 years of being diagnosed as having MM. RESULTS: A total of 34% of patients (N = 123/359) underwent transthoracic echocardiogram and 32% (N = 39/123) had echocardiography-defined PH. PH was significantly associated with older age (70.5 vs 65.3 years; P = 0.019), greater left atrial diameter (4.0 vs 3.7 cm; P = 0.025), and a trend toward decreased renal function. PH was not associated with myeloma-specific features. Fewer patients with PH underwent hematopoietic stem cell transplantation compared with those without PH (10% vs 30%; P = 0.018). There was no significant difference in survival between the PH and non-PH groups (P = 0.2775). CONCLUSIONS: Echocardiography-defined PH was found in a sizeable minority of our MM cohort. Although the specific etiology of PH can be determined only through a prospective clinical evaluation, including right heart catheterization, our results suggest that PH in patients with MM is secondary to left heart disease and perhaps impaired renal function. Patients with PH were significantly less likely to undergo hematopoietic stem cell transplantation. Future studies should assess the etiology of PH, its impact on treatment decisions, and prognosis of patients with MM. PMID: 27135723 [PubMed - indexed for MEDLINE]
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Related Articles Filgrastim-Induced Crescentic Transformation of Recurrent IgG2λ GN. J Am Soc Nephrol. 2016 Jul;27(7):1911-5 Authors: Batal I, Markowitz GS, Wong W, Avasare R, Mapara MY, Appel GB, D'Agati VD Abstract Proliferative GN with monoclonal IgG deposits is an increasingly recognized form of GN, but its relation to hematologic malignancy remains poorly understood. Filgrastim, an analog for granulocyte colony-stimulating factor produced by recombinant DNA technology, is frequently used to stimulate bone marrow release of hematopoietic progenitor cells in preparation for stem cell transplant. We report an exceptional case of proliferative GN with monoclonal IgG2λ deposits in a young man whose disease progressed slowly to CKD, which was followed by a preemptive kidney transplant. The patient developed recurrent GN in the allograft and clinically detectable plasma cell neoplasm 9 years after the first renal manifestations. Contemporaneous with filgrastim administration for stem cell mobilization, the patient's slowly progressive GN underwent severe crescentic transformation, leading to rapidly progressive and irreversible allograft failure. This report explores the spectrum of GN with monoclonal IgG deposits and the pathophysiologic role of granulocyte colony-stimulating factor in exacerbation of preexisting GN. PMID: 27147425 [PubMed - indexed for MEDLINE]
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Related Articles Salmonella Infection Enhances Erythropoietin Production by the Kidney and Liver, Which Correlates with Elevated Bacterial Burdens. Infect Immun. 2016 Oct;84(10):2833-41 Authors: Li LX, Benoun JM, Weiskopf K, Garcia KC, McSorley SJ Abstract Salmonella infection profoundly affects host erythroid development, but the mechanisms responsible for this effect remain poorly understood. We monitored the impact of Salmonella infection on erythroid development and found that systemic infection induced anemia, splenomegaly, elevated erythropoietin (EPO) levels, and extramedullary erythropoiesis in a process independent of Salmonella pathogenicity island 2 (SPI2) or flagellin. The circulating EPO level was also constitutively higher in mice lacking the expression of signal-regulatory protein α (SIRPα). The expression level of EPO mRNA was elevated in the kidney and liver but not increased in the spleens of infected mice despite the presence of extramedullary erythropoiesis in this tissue. In contrast to data from a previous report, mice lacking EPO receptor (EPOR) expression on nonerythroid cells (EPOR rescued) had bacterial loads similar to those of wild-type mice following Salmonella infection. Indeed, treatment to reduce splenic erythroblasts and mature red blood cells correlated with elevated bacterial burdens, implying that extramedullary erythropoiesis benefits the host. Together, these findings emphasize the profound effect of Salmonella infection on erythroid development and suggest that the modulation of erythroid development has both positive and negative consequences for host immunity. PMID: 27456828 [PubMed - indexed for MEDLINE]
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