No abstract

The epithelial tight junction (TJ) has three major functions. As a "gate," it serves as a regulatory barrier separating and maintaining biological fluid compartments of different composition. As a "fence," it generates and maintains the apicobasal polarity of cells that form the confluent epithelium. Finally, the TJ proteins form a trafficking and signaling platform that regulates cell growth, proliferation, differentiation, and dedifferentiation. Six examples are selected that illustrate the emerging link between TJ dysfunction and kidney disease. First, the glomerular slit diaphragm (GSD) is evolved, in part, from the TJ and, on maturation, exhibits all three functions of the TJ. GSD dysfunction leads to proteinuria and, in some instances, podocyte dedifferentiation and proliferation. Second, accumulating evidence supports epithelial-mesenchymal transformation (EMT) as a major player in renal fibrosis, the final common pathway that leads to end-stage renal failure. EMT is characterized by a loss of cell-cell contact and apicobasal polarity, which are hallmarks of TJ dysfunction. Third, in autosomal dominant polycystic kidney disease, mutations of the polycystins may disrupt their known interactions with the apical junction complex, of which the TJ is a major component. This can lead to disturbances in epithelial polarity regulation with consequent abnormal tubulogenesis and cyst formation. Fourth, evidence for epithelial barrier and polarity dysregulation in the pathogenesis of ischemic acute renal failure will be summarized. Fifth, the association between mutations of paracellin-1, the first TJ channel identified, and clinical disorders of magnesium and calcium wasting and bovine renal fibrosis will be used to highlight an integral TJ protein that can serve multiple TJ functions. Finally, the role of WNK4 protein kinase in shunting chloride across the TJ of the distal nephron will be addressed.

Using OPTN/UNOS database, we identified risk factors for development of NODM. Some of these factors are potentially modifiable, including obesity, HCV infection, and the use of tacrolimus. Clinical trials are needed to assess whether modifying these "modifiable risk factors" will indeed prevent NODM.

COVID-19 is a severe infectious disease that has claimed >150,000 lives and infected millions in the United States thus far, especially the elderly population. Emerging evidence has shown the virus to cause hemorrhagic and immunologic responses, which impact all organs, including lungs, kidneys, and the brain, as well as extremities. SARS-CoV-2 also affects patients’, families’, and society’s mental health at large. There is growing evidence of re-infection in some patients. The goal of this paper is to provide a comprehensive review of SARS-CoV-2-induced disease, its mechanism of infection, diagnostics, therapeutics, and treatment strategies, while also focusing on less attended aspects by previous studies, including nutritional support, psychological, and rehabilitation of the pandemic and its management. We performed a systematic review of >1,000 articles and included 425 references from online databases, including, PubMed, Google Scholar, and California Baptist University’s library. COVID-19 patients go through acute respiratory distress syndrome, cytokine storm, acute hypercoagulable state, and autonomic dysfunction, which must be managed by a multidisciplinary team including nursing, nutrition, and rehabilitation. The elderly population and those who are suffering from Alzheimer’s disease and dementia related illnesses seem to be at the higher risk. There are 28 vaccines under development, and new treatment strategies/protocols are being investigated. The future management for COVID-19 should include B-cell and T-cell immunotherapy in combination with emerging prophylaxis. The mental health and illness aspect of COVID-19 are among the most important side effects of this pandemic which requires a national plan for prevention, diagnosis and treatment.

Conclusions: Despite more transplants from older donors and among older recipients, LDKT was associated with superior outcomes compared with SPKT and was coupled with the least wait time and dialysis exposure. LDKT utilization should be considered in all type I diabetics with an available living donor, particularly given the challenges of ongoing organ shortage.

Summary There is an increase in the older incident end-stage renal disease population that is associated with an increasing prevalence of end-stage renal disease in the United States. This trend is paralleled by an increasing rate of kidney transplantation in the elderly. Although patient survival is lower in older versus younger kidney recipients, the elderly benefit from a reduction in mortality rate and improved quality of life with transplantation compared with dialysis. Immunologic, physiologic, and psychosocial factors influence transplant outcomes and should be recognized in the care of the elderly transplant patient. In this review, we discuss transplantation in the elderly patient, particularly the topics of access to transplantation, patient and graft survival, the impact of donor quality on transplant outcomes, immunology and immunosuppression of aging, and ethical considerations in the development of an equitable organ allocation scheme.

Background Recent studies show a survival advantage with kidney transplant amongst elderly patients compared to those on dialysis. Study Design In our present study we examined and compared the association of expanded donor criteria (ECD) kidney and living kidney donation with outcome of kidney transplant across different ages including elderly recipients. Setting and Participants Using the Scientific Registry of Transplant Recipients, we identified 145,470 adult kidney transplanted patients. Mortality and death-censored graft failure risks were estimated by Cox proportional regression analyses over a follow-up period with a median of 3.9 years. Predictors ECD kidney and living kidney donation and age compared to others. Outcomes Mortality and death-censored graft failure risk. Results Patients were 45±16 years old and included 40% women and 19% diabetics. Compared to transplanted patients 55-<65 years old, the fully adjusted death-censored graft failure risk was somewhat higher in patients ≥75 years old (HR, 1.30; 95% CI, 1.09–1.56), 35-<55 years (HR, 1.13; 95% CI, 1.08–1.17) and 18-<35 years (HR, 1.64; 95% CI, 1.57–1.71). Compared to non-ECD kidneys, ECD kidneys were significant predictors of mortality in non-elderly patients (18–<35 years: HR, 1.46 [95% CI, 1.19–1.77]; 35-<55 years: HR, 1.23 [95% CI, 1.14–1.32]; and 55-<65 years: HR, 1.26 [95% CI, 1.15–1.38]) and patients aged 65-<70 years (HR, 1.20; 9% CI, 1.05–1.36); but not in other groups of elderly patients (HRs of 1.12 [95% CI, 0.93–1.36] 70-<75 years and 1.04 [95% CI, 0.74–1.47] for ≥75 years). Similar results were found in risk of graft loss. Compared to deceased donor, living kidney was associated with better survival in all age groups and lower graft loss risk in patients aged <70 years. Limitations Unmeasured confounders cannot be adjusted for. Conclusions Among deceased donors, the ECD kidneys are not associated with either increased mortality or graft failure in recipients over 70 years. Among all types of donors, the persistent association between living donor kidneys and lower all-cause mortality across all ages suggests that, if possible, elderly patients gain longevity from living donor kidney transplant.

Our study suggests that the select group of insured nonresident aliens who undergo transplantation with Medicaid do just as well as US citizens with Medicaid. Policymakers should consider expanding coverage for kidney transplantation in nonresident aliens, including undocumented immigrants, given the associated high-quality outcomes in these patients.