Glucose-lowering agents for treating pre-existing and new-onset diabetes in kidney transplant recipients.
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ABSTRACT:
SUBMITTER: Lo C
PROVIDER: S-EPMC8477618 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Introduction:Secondary hyperparathyroidism (SHPT) and vitamin D deficiency are common at kidney transplantation and are associated with some early and late complications. This study was designed to evaluate whether paricalcitol was more effective than nutritional vitamin D for controlling SHPT in de novo kidney allograft recipients. Methods:This was a 6-month, investigator-initiated, multicenter, open-label, randomized clinical trial. Patients with pretransplantation iPTH between 250 and 600 pg/ml and calcium <10 mg/dl were randomized to paricalcitol (PAR) or calcifediol (CAL). The intention-to-treat population (PAR: n = 46; CAL: n = 47) was used for the analysis. The primary endpoint was the percentage of patients with serum iPTH >110 pg/ml at 6 months. Secondary endpoints were bone mineral metabolism, renal function, and allograft protocol biopsies. Results:The primary outcome occurred in 19.6% of patients in the PAR group and 36.2% of patients in the CAL group (P = 0.07). However, there was a higher percentage of patients with iPTH <70 pg/ml in the PAR group than in the CAL group (63.4% vs. 37.2%; P = 0.03). No differences were observed in bone turnover biomarkers and bone mineral density. The estimated glomerular filtration rate was significantly higher in the CAL group than in the PAR group without differences in albuminuria. In protocol biopsies, interstitial fibrosis and tubular atrophy tended to be higher in the PAR group than in the CAL group (48% vs. 23.8%; P = 0.09). Both medications were well tolerated. Conclusion:Both PAR and CAL reduced iPTH, but PAR was associated with a higher proportion of patients with iPTH <70 pg/ml. These results do not support the use of PAR to treat posttransplantation hyperparathyroidism.
| S-EPMC5762965 | biostudies-literature
Project description:It is well known that pre-transplant B cell activating factor (BAFF) levels are associated with the development of de novo anti-HLA antibodies and antibody mediated rejection post-transplant. However, the clinical significance of BAFF values at allograft rejection has not been determined. In this study, we investigated the clinical significance of pre-transplant BAFF level as well as post-transplant BAFF levels measured when indication biopsy was done. We checked for anti-HLA antibodies in 115 kidney transplant recipients who required allograft biopsy due to an increase in serum creatinine. With the same serum specimen, we measured BAFF levels, and in 78 of these patients, pre-transplant BAFF and anti-HLA antibody levels were detected as well. Patients in each group were divided into tertiles according to BAFF levels. We investigated the relationship between BAFF levels and the occurrence of anti-HLA antibodies. Pre-transplant BAFF levels showed significant association with pre-transplant sensitization, and also with early rejection (Tertile 3, 26.9% vs. Tertile 1, 11.5%; P<0.05). Post-transplant BAFF levels showed significant association with pre-transplant sensitization, but did not show association with anti-HLA antibodies and positive donor-specific antibodies at the time of biopsy. We did not find any association between post-transplant BAFF levels and allograft biopsy results, Banff scores and microvascular inflammation scores. In conclusion, pre-transplant BAFF levels are associated with pre-transplant sensitization and are useful in predicting allograft rejection. But post-transplant BAFF levels measured at the time of indication biopsy are not associated with the appearance of de novo HLA-DSA, allograft rejection, biopsy findings and other allograft outcomes.
| S-EPMC5025051 | biostudies-literature
Project description:The escalating amount of kidney transplant recipients (KTRs) represents a significant dilemma for primary care providers. As the number of physician assistants (PAs) has been steadily increasing in primary care in the United States, the utilization of these healthcare professionals presents a solution for the care of post-kidney transplant recipients. A physician assistant (PA) is a state licensed healthcare professional who practices medicine under physician supervision and can alleviate some of the increasing demands for primary patient care. Here we provide an outline of the crucial components and considerations for PAs caring for kidney transplant recipients. These include renal function and routine screenings, drug monitoring (both immunosuppressive and therapeutic), pre-existing and co-existing conditions, immunizations, nutrition, physical activity, infection, cancer, and the patient's emotional well-being. PAs should routinely monitor renal function and blood chemistry of KTRs. Drug monitoring of KTRs is a crucial responsibility of the PA because of the possible side-effects and potential drug-drug interactions. Therefore, PAs should obtain a careful and detailed patient history from KTRs. PAs should be aware of pre- and co-existing conditions of KTRs as this impacts treatment decisions. Regarding immunization, PAs should avoid administering vaccines containing live or attenuated viruses to KTRs. Because obesity following kidney transplantation is associated with decreased allograft survival, PAs should encourage KTRs to maintain a balanced diet with limited sugar. In addition, KTRs should be urged to gradually increase their levels of physical activity over subsequent years following surgery. PAs should be aware that immunosuppressive medications diminish immune defenses and make KTRs more susceptible to bacterial, viral, and fungal infections. Moreover, KTRs should be screened routinely for cancer due to the higher risk of development from immunosuppressive therapy. PAs must remain cognizant of the emotional well-being of the KTR, as many transplant patients struggle with fear, frustration, and acceptance.
| S-EPMC4677824 | biostudies-literature
Project description:Delayed graft function (DGF) complicates kidney allograft outcomes in the immediate post-transplantation period. We hypothesized that in hemodialysis patients more severe anemia, iron deficiency, the requirement for higher doses of erythropoietin-stimulating agents (ESA), or blood transfusions prior to transplantation are associated with higher risk of DGF.Linking five-yr hemodialysis patient data of a large dialysis organization to the Scientific Registry of Transplant Recipients, we identified 11 836 hemodialysis patients. Using logistic regression analyses we examined the association between pre-transplant parameters and post-transplant DGF.Patients were 49 ± 14 (mean ± SD) yr old and included 38% women, 27% blacks, and 26% diabetics. After adjusting for relevant covariates, pre-transplant blood transfusion was associated with 33% higher DGF risk (odds ratio [OR] = 1.33; 95% confidence interval [CI]: 1.19-1.48); and each 5000 U/wk increase of pre-transplant ESA dose with 5% higher DGF (OR = 1.05; 95% CI: 1.02-1.09). Compared to pre-transplant blood hemoglobin of 12-12.99 g/dL, there was 25% higher risk of DGF with blood hemoglobin 10-10.99 g/dL (OR = 1.25; 95% CI: 1.01-1.55), whereas blood hemoglobin ?13 g/dL exhibited 15% higher risk of DGF (OR = 1.15; 95% CI: 0.98-1.34).Pre-transplant blood transfusion, higher ESA dose, and either high or low blood hemoglobin but not iron markers are associated with higher risk of DGF.
| S-EPMC4571494 | biostudies-literature
Project description:Post-transplant hyperglycemia and new-onset diabetes mellitus after transplantation (NODAT) are common and important metabolic complications. Decreased insulin secretion and increased insulin resistance are important to the pathophysiologic mechanism behind NODAT. However, the progression of glucose intolerance diagnosed late after kidney transplantation remains clearly unknown. Enrolled in this study were 94 kidney transplant recipients and 134 kidney transplant donors, as the healthy controls, who were treated at our institution. The 75 g-oral glucose tolerance test (OGTT) was performed in the recipients, and the healthy controls received an OGTT before donor nephrectomy. We assessed the prevalence of glucose intolerance including impaired fasting glucose and/or impaired glucose tolerance, as well as insulin secretion and insulin resistance using the homeostasis model assessment, and compared the results between the two groups. Multivariate analysis after adjustment for age, gender, body mass index, estimated glomerular filtration rate, and systolic blood pressure showed that the prevalence of glucose intolerance, insulin resistance, insulin secretion, and 2 h plasma glucose levels were significantly higher in the kidney transplant recipients compared to the healthy controls. Elevation of insulin secretion in kidney transplant recipients may be compensatory for increase of insulin resistance. Impaired compensatory pancreas β cell function may lead to glucose intolerance and NODAT in the future.
| S-EPMC6678426 | biostudies-literature
Project description:BK polyomavirus (BKPyV) reactivation in kidney transplant recipients can lead to allograft damage and loss. The elements of the adaptive immune system that are permissive of reactivation and responsible for viral control remain incompletely described. We performed a prospective study evaluating BKPyV-specific T-cell response, humoral response and overall T-cell phenotype beginning pre-transplant through one year post-transplant in 28 patients at two centers. We performed an exploratory analysis of risk factors for the development of viremia and viruria as well as compared the immune response to BKPyV in these groups and those who remained BK negative. 6 patients developed viruria and 3 developed viremia. BKPyV-specific CD8+ T-cells increased post-transplant in viremic and viruric but not BK negative patients. BKPyV-specific CD4+ T-cells increased in viremic, but not viruric or BK negative patients. Anti-BKPyV IgG antibodies increased in viruric and viremic patients but remained unchanged in BK negative patients. Viremic patients had a greater proportion of CD8+ effector cells pre-transplant and at 12 months post-transplant. Viremic patients had fewer CD4+ effector memory cells at 3 months post-transplant. Exploratory analysis demonstrated lower CD4 and higher total CD8 proportions, higher anti-BKPyV antibody titers and the cause of renal failure were associated BKPyV reactivation. In conclusion, low CD4, high CD8 and increased effector CD8 cells were found pre-transplant in patients who became viremic, a phenotype associated with immune senescence. This pre-transplant T-cell senescence phenotype could potentially be used to identify patients at increased risk of BKPyV reactivation.
| S-EPMC5451008 | biostudies-literature
Project description:Older kidney transplant recipients are susceptible to cognitive impairment, frailty, comorbidities, immunosuppression-related complications, and chronic graft failure, however, there has been limited focus on their concerns and expectations related to transplantation. This study aims to describe the perspectives of older kidney transplant recipients about their experience of kidney transplantation, self-management, and treatment goals to inform strategies and interventions that address their specific needs.Face-to-face semistructured interviews were conducted with 30 kidney transplant recipients aged 65-80 years from five renal units in Australia. Transcripts were analyzed thematically.Six themes were identified: restoring vitality of youth (with subthemes of revived mindset for resilience, embracing enjoyment in life, drive for self-actualization); persisting through prolonged recovery (yielding to aging, accepting functional limitations, pushing the limit, enduring treatment responsibilities); imposing sicknesses (combatting devastating comorbidities, painful restrictions, emerging disillusionment, anxieties about accumulating side effects, consuming treatment burden); prioritizing graft survival (privileged with a miracle, negotiating risks for longevity, enacting a moral duty, preserving the last opportunity); confronting health deterioration (vulnerability and helplessness, narrowing focus to immediate concerns, uncertainty of survival); and value of existence (purpose through autonomy, refusing the burden of futile treatment, staying alive by all means).Older kidney transplant recipients felt able to enjoy life and strived to live at their newly re-established potential and capability, which motivated them to protect their graft. However, some felt constrained by slow recuperation and overwhelmed by unexpected comorbidities, medication-related side effects, and health decline. Our findings suggest the need to prepare and support older recipients for self-management responsibilities, clarify their expectations of post-transplant risks and outcomes, and provide assistance through prolonged recovery after kidney transplantation.
| S-EPMC5338704 | biostudies-other
Project description:Introduction:Sexual dysfunction is a common problem in patients with chronic kidney disease. Disturbances in sexual function are noticed in early stages of chronic kidney diseases and deteriorate further as renal function declines. This is due to uremic effects, comorbid illness, anemia, hormonal disturbances, autonomic neuropathy, vascular diseases, hyperparathyroidism, hyperprolactinemia, side effects of medications, and psychosocial factors. Patients and method:This is a cross-sectional study which included 59 male patients who underwent renal transplantation for more than 6 months. The International Index of Erectile Function (IIEF-5) was adopted in our study to record the erectile function. Results:The mean age was 49.41 years, and the mean number of hemodialysis per month was 5.31. The cause of the chronic kidney disease was diabetes mellitus in 35.59%, glomerulonephritis in 20.34%, and hypertension in 16.95%, other causes were diagnosed in order of decreasing frequency. Most patients developed improvement in the erectile function after transplantation. There was significant correlation with 3 of the elements of the IIFE-5.i.e; penile hardness pre-penetration, Maintaining erection during intercourse, and Difficulty to maintain erection to complete the intercourse (p values 0.015, 0.011, and 0.023) respectively, and the overall improvement after transplantation which showed a p-value of less than 0.031, while there was no significant correlation with Confidence with erection and Satisfaction with intercourse before and after transplantation (p values 0.113 and 0.121) respectively. One of the patients (1.7%) developed severe dysfunction after that. Conclusion:ED is common sequel of chronic kidney disease. The etiology is multifactorial and may be worsen by advanced age, presence of diabetes mellitus and prolonged duration of hemodialysis. Renal transplantation has a positive impact on sexual function and lead to improvement of erectile dysfunction. Erectile dysfunction that persists after kidney transplantation is usually attributed to multiple preexisting comorbidities.
| S-EPMC7251300 | biostudies-literature
Project description:Costimulation between T cells and antigen-presenting cells is essential for the regulation of an effective alloimmune response and is not targeted with the conventional immunosuppressive therapy after kidney transplantation. Costimulation blockade therapy with biologicals allows precise targeting of the immune response but without non-immune adverse events. Multiple costimulation blockade approaches have been developed that inhibit the alloimmune response in kidney transplant recipients with varying degrees of success. Belatacept, an immunosuppressive drug that selectively targets the CD28-CD80/CD86 pathway, is the only costimulation blockade therapy that is currently approved for kidney transplant recipients. In the last decade, belatacept therapy has been shown to be a promising therapy in subgroups of kidney transplant recipients; however, the widespread use of belatacept has been tempered by an increased risk of acute kidney transplant rejection. The purpose of this review is to provide an overview of the costimulation blockade therapies that are currently in use or being developed for kidney transplant indications.
| S-EPMC6978297 | biostudies-literature
Project description:METHODS:Patients transplanted at our institution provided fecal samples before, and 3-9 months after KT. Fecal bacterial DNA was extracted and 9 bacteria or bacterial groups were quantified by qPCR. RESULTS:50 patients (19 controls without diabetes, 15 who developed New Onset Diabetes After Transplantation, NODAT, and 16 with type 2 diabetes before KT) were included. Before KT, Lactobacillus sp. tended to be less frequently detected in controls than in those who would become diabetic following KT (NODAT) and in initially diabetic patients (60%, 87.5%, and 100%, respectively, p = 0.08). The relative abundance of Faecalibacterium prausnitzii was 30 times lower in initially diabetic patients than in controls (p = 0.002). The relative abundance of F. prausnitzii of NODAT patients was statistically indistinguishable from controls and from diabetic patients. The relative abundance of Lactobacillus sp. increased following KT in NODAT and in initially diabetic patients (20-fold, p = 0.06, and 25-fold, p = 0.02, respectively). In contrast, the proportion of Akkermansia muciniphila decreased following KT in NODAT and in initially diabetic patients (2,500-fold, p = 0.04, and 50,000-fold, p<0.0001, respectively). The proportion of Lactobacillus and A. muciniphila did not change in controls between before and after the transplantation. Consequently, after KT the relative abundance of Lactobacillus sp. was 25 times higher (p = 0.07) and the relative abundance of A. muciniphila was 2,000 times lower (p = 0.002) in diabetics than in controls. CONCLUSION:An alteration of the gut microbiota composition involving Lactobacillus sp., A. muciniphila and F. prausnitzii is associated with the glycemic status in KT recipients, raising the question of their role in the genesis of NODAT.
| S-EPMC6946168 | biostudies-literature