Kidney Transplantation in Children Dharnidharka, Vikas R; Fiorina, Paolo; Harmon, William E
New England journal of medicine/The New England journal of medicine,
08/2014, Volume:
371, Issue:
6
Journal Article
Peer reviewed
Open access
This review discusses unique aspects of kidney transplantation in children that necessitate specialized approaches and have resulted in clinical advances so that kidney transplantations in young ...children have higher success rates than in any other age group.
Since the first successful kidney transplantation in 1954,
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kidney transplantation has become the best treatment for adult patients with kidney failure. However, early pediatric kidney transplantation was complicated by technical, immunologic, and logistic problems, all leading to worse patient and graft survival among children than had been observed among adults. Over the past 15 years, a number of advances have greatly improved patient and graft survival among children with kidney transplants.
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,
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Some aspects of clinical kidney transplantation are similar in children and adults. The immunosuppressive medications and regimens used are similar, creatinine is the major serum biomarker, acute rejection . . .
Aims
SARS–CoV-2 causes severe respiratory syndrome (COVID-19) with high mortality due to a direct cytotoxic viral effect and a severe systemic inflammation. We are herein discussing a possible novel ...therapeutic tool for COVID-19.
Methods
Virus binds to the cell surface receptor ACE2; indeed, recent evidences suggested that SARS–CoV-2 may be using as co-receptor, when entering the cells, the same one used by MERS–Co-V, namely the DPP4/CD26 receptor. The aforementioned observation underlined that mechanism of cell entry is supposedly similar among different coronavirus, that the co-expression of ACE2 and DPP4/CD26 could identify those cells targeted by different human coronaviruses and that clinical complications may be similar.
Results
The DPP4 family/system was implicated in various physiological processes and diseases of the immune system, and DPP4/CD26 is variously expressed on epithelia and endothelia of the systemic vasculature, lung, kidney, small intestine and heart. In particular, DPP4 distribution in the human respiratory tract may facilitate the entrance of the virus into the airway tract itself and could contribute to the development of cytokine storm and immunopathology in causing fatal COVID-19 pneumonia.
Conclusions
The use of DPP4 inhibitors, such as gliptins, in patients with COVID-19 with, or even without, type 2 diabetes, may offer a simple way to reduce the virus entry and replication into the airways and to hamper the sustained cytokine storm and inflammation within the lung in patients diagnosed with COVID-19 infection.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Chronic inflammation is postulated to be involved in the development of end-stage renal disease in diabetes, but which specific circulating inflammatory proteins contribute to this risk remain ...unknown. To study this, we examined 194 circulating inflammatory proteins in subjects from three independent cohorts with type 1 and type 2 diabetes. In each cohort, we identified an extremely robust kidney risk inflammatory signature (KRIS), consisting of 17 proteins enriched in tumor necrosis factor-receptor superfamily members, that was associated with a 10-year risk of end-stage renal disease. All these proteins had a systemic, non-kidney source. Our prospective study findings provide strong evidence that KRIS proteins contribute to the inflammatory process underlying end-stage renal disease development in both types of diabetes. These proteins point to new therapeutic targets and new prognostic tests to identify subjects at risk of end-stage renal disease, as well as biomarkers to measure responses to treatment of diabetic kidney disease.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This report describes five patients with treatment-resistant focal segmental glomerulosclerosis and positive B7-1 immunostaining who had a response to abatacept (CTLA-4–Ig), a costimulatory inhibitor ...that targets B7-1 (CD80).
The renal glomeruli are highly specialized structures that ensure selective ultrafiltration of plasma, by which most proteins are retained in the blood.
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The glomerular filtration barrier consists of the glomerular capillary endothelium, the glomerular basement membrane, and specialized cells, the podocytes, that serve as a final barrier to urinary loss of plasma proteins.
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Disrupted podocyte function damages the kidney filtration mechanism, resulting in proteinuria and, in some circumstances, the nephrotic syndrome.
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Proteinuria is common to a heterogeneous group of kidney diseases, including minimal-change disease, FSGS, membranous nephropathy, and diabetic nephropathy, all of which affect millions of persons worldwide and often . . .
Current approaches aiming to cure type 1 diabetes (T1D) have made a negligible number of patients insulin-independent. In this review, we revisit the role of stem cell (SC)-based applications in ...curing T1D. The optimal therapeutic approach for T1D should ideally preserve the remaining β-cells, restore β-cell function, and protect the replaced insulin-producing cells from autoimmunity. SCs possess immunological and regenerative properties that could be harnessed to improve the treatment of T1D; indeed, SCs may reestablish peripheral tolerance toward β-cells through reshaping of the immune response and inhibition of autoreactive T-cell function. Furthermore, SC-derived insulin-producing cells are capable of engrafting and reversing hyperglycemia in mice. Bone marrow mesenchymal SCs display a hypoimmunogenic phenotype as well as a broad range of immunomodulatory capabilities, they have been shown to cure newly diabetic nonobese diabetic (NOD) mice, and they are currently undergoing evaluation in two clinical trials. Cord blood SCs have been shown to facilitate the generation of regulatory T cells, thereby reverting hyperglycemia in NOD mice. T1D patients treated with cord blood SCs also did not show any adverse reaction in the absence of major effects on glycometabolic control. Although hematopoietic SCs rarely revert hyperglycemia in NOD mice, they exhibit profound immunomodulatory properties in humans; newly hyperglycemic T1D patients have been successfully reverted to normoglycemia with autologous nonmyeloablative hematopoietic SC transplantation. Finally, embryonic SCs also offer exciting prospects because they are able to generate glucose-responsive insulin-producing cells. Easy enthusiasm should be mitigated mainly because of the potential oncogenicity of SCs.
Patients with coronavirus disease 2019 (COVID-19) are reported to have a greater prevalence of hyperglycaemia. Cytokine release as a consequence of severe acute respiratory syndrome coronavirus 2 ...infection may precipitate the onset of metabolic alterations by affecting glucose homeostasis. Here we describe abnormalities in glycometabolic control, insulin resistance and beta cell function in patients with COVID-19 without any pre-existing history or diagnosis of diabetes, and document glycaemic abnormalities in recovered patients 2 months after onset of disease. In a cohort of 551 patients hospitalized for COVID-19 in Italy, we found that 46% of patients were hyperglycaemic, whereas 27% were normoglycaemic. Using clinical assays and continuous glucose monitoring in a subset of patients, we detected altered glycometabolic control, with insulin resistance and an abnormal cytokine profile, even in normoglycaemic patients. Glycaemic abnormalities can be detected for at least 2 months in patients who recovered from COVID-19. Our data demonstrate that COVID-19 is associated with aberrant glycometabolic control, which can persist even after recovery, suggesting that further investigation of metabolic abnormalities in the context of long COVID is warranted.
Type 1 diabetes (T1D) is one of the major autoimmune diseases affecting children and young adults worldwide. To date, the different immunotherapies tested have achieved insulin independence in <5% of ...treated individuals. Recently, a novel hematopoietic stem cell (HSC)-based strategy has been tested in individuals with new-onset T1D. The aim of this study was to determine the effects of autologous nonmyeloablative HSC transplantation in 65 individuals with new-onset T1D who were enrolled in two Chinese centers and one Polish center, pooled, and followed up for 48 months. A total of 59% of individuals with T1D achieved insulin independence within the first 6 months after receiving conditioning immunosuppression therapy (with antithymocyte globulin and cyclophosphamide) and a single infusion of autologous HSCs, and 32% remained insulin independent at the last time point of their follow-up. All treated subjects showed a decrease in HbA1c levels and an increase in C-peptide levels compared with pretreatment. Despite a complete immune system recovery (i.e., leukocyte count) after treatment, 52% of treated individuals experienced adverse effects. Our study suggests the following: 1) that remission of T1D is possible by combining HSC transplantation and immunosuppression; 2) that autologous nonmyeloablative HSC transplantation represents an effective treatment for selected individuals with T1D; and 3) that safer HSC-based therapeutic options are required.
The prevalence of diabetes mellitus is rising among children and adolescents worldwide. Cardiovascular diseases are the main cause of morbidity and mortality in diabetic patients. We review the ...impact of diabetes on establishing, during childhood and adolescence, the premises for cardiovascular diseases later in life. Interestingly, it seems that hyperglycemia is not the only factor that establishes an increased cardiovascular risk in adolescence. Other factors have been recognized to play a role in triggering the onset of latent cardiovascular diseases in the pediatric population. Among these cardiovascular risk factors, some are modifiable: glucose variability, hypoglycemia, obesity, insulin resistance, waist circumference, hypertension, dyslipidemia, smoking alcohol, microalbuminuria and smoking. Others are unmodifiable, such as diabetes duration and family history. Among the etiological factors, subclinical endothelial dysfunction represents one of the earliest key players of atherosclerosis and it can be detected during early ages in patients with diabetes. A better assessment of cardiovascular risk in pediatric population still represents a challenge for clinicians, and thus further efforts are required to properly identify and treat pediatric patients who may suffer from cardiovascular disease later in early adulthood.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Insulin represents a life-saving therapy for patients with type 1 diabetes but, despite appropriate treatment, it prevents only partially long-term diabetic complications, while generating fatal ...hypoglycemic episodes. Islet transplantation gained attention because of its safety, effectiveness, and minimal invasiveness; however it remains a procedure reserved for a selected group of patients. The introduction of the Edmonton Protocol in 2000, based on a newly designed steroid-free immunosuppressive protocol, revamped the course of islet transplantation. The main goal of islet transplantation remains insulin independence, although the effect of islet transplantation can be more comprehensively evaluated in terms of frequency of hypoglycemic episodes and impact on diabetic complications and quality of life. Islet transplantation was shown to have positive consequences on cardiovascular, renal, neurologic, and ocular diabetic complications. The proof of concept for cellular replacement therapy in diabetes has been established with islet transplantation, it only needs to be improved and rendered widely available.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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