scholarly journals Targeting Mitochondria during Cold Storage to Maintain Proteasome Function and Improve Renal Outcome after Transplantation

2020 ◽  
Vol 21 (10) ◽  
pp. 3506
Author(s):  
Sorena B. Lo ◽  
Richard T. Blaszak ◽  
Nirmala Parajuli

Kidney transplantation is the preferred treatment for end-stage kidney disease (ESKD). Compared to maintenance dialysis, kidney transplantation results in improved patient survival and quality of life. Kidneys from living donors perform best; however, many patients with ESKD depend on kidneys from deceased donors. After procurement, donor kidneys are placed in a cold-storage solution until a suitable recipient is located. Sadly, prolonged cold storage times are associated with inferior transplant outcomes; therefore, in most situations when considering donor kidneys, long cold-storage times are avoided. The identification of novel mechanisms of cold-storage-related renal damage will lead to the development of new therapeutic strategies for preserving donor kidneys; to date, these mechanisms remain poorly understood. In this review, we discuss the importance of mitochondrial and proteasome function, protein homeostasis, and renal recovery during stress from cold storage plus transplantation. Additionally, we discuss novel targets for therapeutic intervention to improve renal outcomes.

2020 ◽  
Vol 35 (4) ◽  
pp. 687-696
Author(s):  
Jimena Cabrera ◽  
Mario Fernández-Ruiz ◽  
Hernando Trujillo ◽  
Esther González ◽  
María Molina ◽  
...  

Abstract Background Advances in life expectancy have led to an increase in the number of elderly people with end-stage renal disease (ESRD). Scarce information is available on the outcomes of kidney transplantation (KT) in extremely elderly patients based on an allocation policy prioritizing donor–recipient age matching. Methods We included recipients ≥75 years that underwent KT from similarly aged deceased donors at our institution between 2002 and 2015. Determinants of death-censored graft and patient survival were assessed by Cox regression. Results We included 138 recipients with a median follow-up of 38.8 months. Median (interquartile range) age of recipients and donors was 77.5 (76.3–79.7) and 77.0 years (74.7–79.0), with 22.5% of donors ≥80 years. Primary graft non-function occurred in 8.0% (11/138) of patients. Cumulative incidence rates for post-transplant infection and biopsy-proven acute rejection (BPAR) were 70.3% (97/138) and 15.2% (21/138), respectively. One- and 5-year patient survival were 82.1 and 60.1%, respectively, whereas the corresponding rates for death-censored graft survival were 95.6 and 93.1%. Infection was the leading cause of death (46.0% of fatal cases). The occurrence of BPAR was associated with lower 1-year patient survival [hazard ratio (HR) = 4.21, 95% confidence interval (CI) 1.64–10.82; P = 0.003]. Diabetic nephropathy was the only factor predicting 5-year death-censored graft survival (HR = 4.82, 95% CI 1.08–21.56; P = 0.040). Conclusions ESRD patients ≥75 years can access KT and remain dialysis free for their remaining lifespan by using grafts from extremely aged deceased donors, yielding encouraging results in terms of recipient and graft survival.


2021 ◽  
Vol 8 ◽  
pp. 233339282110183
Author(s):  
Tariku Shimels ◽  
Abrham Getachew ◽  
Mekdim Tadesse ◽  
Alison Thompson

Introduction: Transplantation is the optimal management for patients with end-stage renal disease. In Ethiopia, the first national kidney transplantation center was opened at St. Paul’s Hospital Millennium Medical College in September 2015. The aim of this study was to explore providers’ views and experiences of the past to present at this center. Methods: A qualitative study design was employed from 1st November to 15th December, 2019. To ensure that appropriate informants would provide rich study data, 8 health care providers and top management members were purposefully chosen for in-depth interviews. A maximum variation sampling method was considered to include a representative sample of informants. Interviews were digitally audio-recorded, and transcribed verbatim. Transcribed data was coded and analyzed using Qualitative Data Analysis (QDA) Minor Lite software and Microsoft-Excel. Result: The participants (5 males and 3 females) approached were from different departments of the renal transplant center, and the main hospital. Eight main themes and 18 sub-themes were generated initially from all interviews totaling to 109 index codes. Further evaluation and recoding retained 5 main themes, and 14 sub-themes. The main themes are; challenges experienced during and after launching the center, commitment, sympathy and satisfaction, outcomes of renal transplant, actions to improve the quality of service, and how the transplant center should operate. Providers claim that they discharge their responsibilities through proper commitment and compassion, paying no attention to incentive packages. They also explained that renal transplantation would have all the outcomes related to economic, humanistic and clinical facets. Conclusion and Recommendation: A multitude of challenges were faced during and after the establishment of the first renal transplant center in Ethiopia. Providers discharge their responsibility through a proper compassion for patients. Concerned stakeholders should actively collaborate to improve the quality of renal transplant services in the center.


2020 ◽  
Vol 31 (1) ◽  
pp. 1-15
Author(s):  
Onesmo A. Kisanga ◽  
Francis F. Furia ◽  
Paschal J. Ruggajo ◽  
Eden E. Maro

Background: Renal replacement therapy (RRT), which includes dialysis and kidney transplantation, is the treatment of choice for patients with end stage renal failure (ESRF). Most sub-Saharan African countries have not developed renal transplantation services and are relying on referring patients to overseas countries. This study was carried out to describe renal transplantation experience in Tanzania.Methods: Forty-four renal transplant recipients were recruited in this study. Standardized questionnaire and Swahili version of standard form – 36 (SF-36) were used to collect socio-demographic information, clinical data, laboratory test results and health related quality of life information.Results: Ages of transplant recipient ranged from 21 to 66 years with mean age of 45.9 ± 10.5 years. The leading causes of end stage renal failure among participants was hypertension 58.8% (25/44) followed by glomerulonephritis 15.9% (7/44). Twentyeight (63.6%) of transplantations were paid by the government. Most of the donors (97.7%) were living out of which 26 (59.1%) were siblings and 11 (25%) were second-degree relatives (cousins and nephews). Most common complication noted following transplantation was diabetes mellitus 9 (20.5%) and 3 (6.8%) had chronic rejection. Mental health was the domain with highest mean score (75.6 ± 14.3) and role physical had the least mean score (44 ± 45.6).Conclusions:  Hypertension was the leading cause of ESRF in this study. Most of the donors were siblings and the costs of transplantation were largely covered by the government. There is a need for concerted effort to establish local kidney transplantation services in Tanzania. Keywords: Renal transplantation, quality of life in transplantation, Tanzania.


Diabetologia ◽  
2013 ◽  
Vol 56 (6) ◽  
pp. 1364-1371 ◽  
Author(s):  
J. P. Lindahl ◽  
A. Hartmann ◽  
R. Horneland ◽  
H. Holdaas ◽  
A. V. Reisæter ◽  
...  

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Gregory J. Wilson ◽  
Yeoungjee Cho ◽  
Armando Teixiera-Pinto ◽  
Nicole Isbel ◽  
Scott Campbell ◽  
...  

Abstract Background Membranoproliferative glomerulonephritis (MPGN) is an uncommon cause of end stage kidney disease (ESKD) and the clinical outcomes of patients with MPGN who commence kidney replacement therapy have not been comprehensively studied. Methods All adult patients with ESKD due to glomerulonephritis commencing kidney replacement therapy in Australia and New Zealand from January 1, 1996 to December 31, 2016 were reviewed. Patients with ESKD due to MPGN were compared to patients with other forms of glomerulonephritis. Patient survival on dialysis and following kidney transplantation, kidney recovery on dialysis, time to transplantation, allograft survival, death-censored allograft survival and disease recurrence post-transplant were compared between the two groups using Kaplan Meier survival curves and Cox proportional hazards regression. Results Of 56,481 patients included, 456 (0.8%) had MPGN and 12,660 (22.4%) had another form of glomerulonephritis. Five-year patient survival on dialysis and following kidney transplantation were similar between patients with ESKD from MPGN and other forms of glomerulonephritis (Dialysis: 59% vs. 62% p = 0.61; Transplant: 93% vs. 93%, p = 0.49). Compared to patients with other forms of glomerulonephritis, patients with MPGN had significantly poorer 5-year allograft survival (70% vs. 81% respectively, p = 0.02) and death censored allograft survival (74% vs. 87%, respectively; p < 0.01). The risk of disease recurrence was significantly higher in patients with MPGN compared to patients with other glomerulonephritidites (18% vs. 5%; p < 0.01). In patients with MPGN who had allograft loss, patients with MPGN recurrence had a significantly shorter time to allograft loss compared to patients with MPGN who had allograft loss due to any other cause (median time to allograft loss 3.2 years vs. 4.4 years, p < 0.01). Conclusions Compared with other forms of glomerulonephritis, patients with MPGN experienced comparable rates of survival on dialysis and following kidney transplantation, but significantly higher rates of allograft loss due to disease recurrence.


2020 ◽  
Vol 38 ◽  
Author(s):  
Ana Amélia Fayer Rotella ◽  
Rosemeire Aparecida do Nascimento ◽  
Maria Fernanda Carvalho de Camargo ◽  
Paulo Cesar Koch Nogueira

ABSTRACT Objective: To investigate the emotional repercussions and quality of life (QOL) associated with end-stage kidney disease (ESKD) in children and adolescents undergoing hemodialysis or a kidney transplant (TX). Methods: We conducted a quantitative-qualitative study. 48 children and adolescents with ESKD were interviewed; half of them underwent hemodialysis treatment, and the other half had a kidney transplantation. Their respective 48 caregivers also participated in the study. The questionnaire involved both the Pediatric Quality of Life Inventory and a thematic story-drawing tool. An analysis of the QOL questionnaire’s results was done by comparing the sum of points between groups and the theme-based story-drawing consisted of interpreting the data contained in the material using Freudian and Lacanian theories. Results: In the QOL questionnaires, the total score was higher in the transplanted patients and in their caregivers, suggesting a perception of better QOL after kidney transplantation. In the specific aspects of the questionnaire, physical capacity was considered superior by children who underwent transplants and their caregivers. There were no differences between the groups in the emotional, social and school aspects. However, the caregivers of the patients who had a transplant perceived a significant difference in QOL in the school aspect. In the thematic story-drawings, emotional suffering in the two analyzed groups was evidenced regardless of the treatment. Conclusions: Despite the questionnaire results suggesting that transplantation does improve some aspects of QOL, there were no differences observed between kidney replacement therapies regarding the emotional repercussion of chronic kidney disease.


2020 ◽  
Vol 9 (7) ◽  
pp. 2134
Author(s):  
Taihei Ito ◽  
Takashi Kenmochi ◽  
Naohiro Aida ◽  
Hajime Matsushima ◽  
Kei Kurihara ◽  
...  

Background: The impact of pancreas transplantation, including kidney transplantation on patients’ life prognoses, is unclear in Japan. An analysis of the data of the Japan Pancreas Transplant Registry was performed to compare the patient survival between on the waiting list and after pancreas transplantation, and investigate the factors that affect the patient survival after pancreatic transplantation. Methods: The life prognoses of 361 patients who underwent pancreas transplantation from 2000 to December 2018 were examined. Results: The survival rates at 1, 5, and 10 years on the waiting list were 98.4%, 90.3%, and 78.1%, respectively, while those after transplantation were significantly improved (p = 0.029) at 100%, 97.5%, and 88.9%, respectively. Furthermore, the survival rates of patients waiting for simultaneous pancreas and kidney transplantation (SPK) at 1, 5, and 10 years were 98.2%, 89.4%, and 75.4%, respectively, while those after SPK were also significantly improved (p = 0.026) at 100%, 94.6%, and 88.8%. The multivariable analysis revealed that the duration of diabetes before surgery was the only independent risk factor (hazard ratio = 1.095, p = 0.012) that affected the patient survival after SPK. Conclusion: Pancreas transplantation was found to improve the life prognosis of patients with type 1 diabetes, especially those with end-stage renal failure waiting for SPK.


Blood ◽  
2012 ◽  
Vol 120 (22) ◽  
pp. 4292-4295 ◽  
Author(s):  
Nelson Leung ◽  
Frank Bridoux ◽  
Colin A. Hutchison ◽  
Samih H. Nasr ◽  
Paul Cockwell ◽  
...  

Abstract Multiple myeloma is the most frequent monoclonal gammopathy to involve the kidney; however, a growing number of kidney diseases associated with other monoclonal gammopathies are being recognized. Although many histopathologic patterns exist, they are all distinguished by the monoclonal immunoglobulin (or component) deposits. The hematologic disorder in these patients is more consistent with monoclonal gammopathy of undetermined significance (MGUS) than with multiple myeloma. Unfortunately, due to the limitations of the current diagnostic schema, they are frequently diagnosed as MGUS. Because treatment is not recommended for MGUS, appropriate therapy is commonly withheld. In addition to end-stage renal disease, the persistence of the monoclonal gammopathy is associated with high rates of recurrence after kidney transplantation. Preservation and restoration of kidney function are possible with successful treatment targeting the responsible clone. Achievement of hematologic complete response has been shown to prevent recurrence after kidney transplantation. There is a need for a term that properly conveys the pathologic nature of these diseases. We think the term monoclonal gammopathy of renal significance is most helpful to indicate a causal relationship between the monoclonal gammopathy and the renal damage and because the significance of the monoclonal gammopathy is no longer undetermined.


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