N-acetylcysteine (NAC) has shown beneficial effects in both acute kidney disease and chronic kidney disease (CKD) in preclinical and clinical studies. Different dosage and administration forms of NAC have specific pharmacokinetic properties that determine the temporal pattern of plasma concentrations of NAC and its active metabolites. Especially in acute situations with short-term NAC administration, appropriate NAC and glutathione (GSH) plasma concentrations should be timely ensured.
View Article and Find Full Text PDFThe objective of the present study was to compare principal cell-specific aquaporin-2 (AQP2) abundances in urinary extracellular vesicles (uEVs) on the first postoperative day in deceased-donor kidney transplant recipients without and with acute kidney injury. We measured uEV markers (CD9 and CD63) and the abundances of proximal tubular sodium-glucose transporter 2, distal tubular sodium/chloride cotransporter, and principal cell-specific aquaporin-2 using Western blotting of urine. uEV-AQP2 levels were normalized to living donor controls.
View Article and Find Full Text PDFIntroduction: Periostin is a matricellular protein. Elevated serum concentrations of periostin have been reported in patients with various cardiovascular diseases, including heart failure. Patients with end-stage renal disease have a substantially increased risk for cardiovascular diseases.
View Article and Find Full Text PDFPeripheral blood mononuclear cells contain secretory granules with Perforin and Granzyme B for defense against pathogens. The objective of the present study was to compare the effects of immunosuppressive induction therapies on Perforin and Granzyme B transcripts in kidney transplant recipients. Transcripts were determined in 408 incident kidney transplant recipients eight days posttransplant using quantitative real-time PCR.
View Article and Find Full Text PDFBackground: The renal proximal tubule (RPT) plays a pivotal role in regulating sodium reabsorption and thus blood pressure (BP). Transient receptor potential ankyrin 1 (TRPA1) has been reported to protect against renal injury by modulating mitochondrial function. We hypothesize that the activation of TRPA1 by its agonist cinnamaldehyde may mitigate high-salt intake-induced hypertension by inhibiting urinary sodium reabsorption through restoration of renal tubular epithelial mitochondrial function.
View Article and Find Full Text PDFThe forkhead box P3 (FOXP3) transcript is essential for tolerance of alloantigens. Here, we describe the expression of FOXP3 mRNA variants in healthy females and males, and in kidney transplant recipients (KTR). We measured FOXP3 in peripheral blood mononuclear cells from healthy kidney donors (N = 101), and in blood from KTRs (N = 248) before and after transplantation.
View Article and Find Full Text PDFBackground: Progressive decline of allograft function leads to premature graft loss. Forkhead box P3 (FOXP3), a characteristic gene of T-regulatory cells, is known to be essential for auto-antigen tolerance. We assessed the hypothesis that low FOXP3 mRNA splice variant levels in peripheral blood cells early after transplantation are associated with progressive allograft injury.
View Article and Find Full Text PDFBackground And Aims: Outcome trials using sodium glucose cotransporter type 2 inhibitors have consistently shown their potential to preserve kidney function in diabetic and nondiabetic patients. Several mechanisms have been introduced which may explain the nephroprotective effect of sodium glucose cotransporter type 2 inhibitors beyond lowering blood glucose. This current narrative review has the objective to describe main underlying mechanisms causing a nephroprotective effect and to show similarities as well as differences between proposed mechanisms which can be observed in patients with diabetic and nondiabetic chronic kidney disease.
View Article and Find Full Text PDFForkhead Box P3 (FOXP3) is crucial for the development and suppressive function of human regulatory T cells (Tregs). There are two predominant FOXP3 splicing isoforms in healthy humans, the full-length isoform and the isoform lacking exon 2, with different functions and regulation mechanisms. FOXP3 splicing isoforms show distinct abilities in the cofactor interaction and the nuclear translocation, resulting in different effects on the differentiation, cytokine secretion, suppressive function, linage stability, and environmental adaptation of Tregs.
View Article and Find Full Text PDFBackground: Immunosuppressive treatment of kidney transplant recipients is mainly aimed at pro-inflammatory T effector cells, yet they also target the immunosuppressive T regulatory cells. Here, we test the hypothesis that low levels of the master gene regulator of T regulatory cells, forkhead box P3 (FOXP3) splice variants, are associated with prolonged inflammatory responses to stimuli.
Methods: From blood samples obtained the first - and 29 day post-transplant, we extracted peripheral blood mononuclear cells and measured mRNA levels of Total FOXP3, pre-mature RNA FOXP3 (pre-mRNA FOXP3), full length FOXP3 (FOXP3fl) and, FOXP3 splice variant excluding exon two (FOXP3d2).
Early prediction of kidney graft function may assist clinical management, and for this, reliable non-invasive biomarkers are needed. We evaluated endotrophin (ETP), a novel non-invasive biomarker of collagen type VI formation, as a prognostic marker in kidney transplant recipients. ETP levels were measured with the PRO-C6 ELISA in the plasma (P-ETP) of 218 and urine (U-ETP/Cr) of 172 kidney transplant recipients, one (D1) and five (D5) days, as well as three (M3) and twelve (M12) months, after transplantation.
View Article and Find Full Text PDFBackground: This case report highlights a successful steroid-free, low-dose immunosuppressive protocol for renal transplantation in a pediatric patient with Schimke immuno-osseous dysplasia with excellent 7-year patient and graft survival. Schimke immuno-osseous dysplasia is a rare multisystem disorder involving the kidney. Renal transplantation is a therapeutic option, but posttransplant mortality is high due to severe infections and posttransplant lymphoproliferative disease.
View Article and Find Full Text PDFBackground: Fibrosis is a suggested cause of graft failure and mortality among kidney transplant recipients (KTRs). Accumulating evidence suggests that collagen type VI is tightly linked to fibrosis and may be a marker of systemic fibrosis and ageing. We studied whether plasma endotrophin, a pro-collagen type VI fragment, is associated with graft failure and mortality among KTRs.
View Article and Find Full Text PDFOxidative stress (OS) presents even in the early chronic kidney disease (CKD) stage and is exacerbated in patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis (MHD). There is still a debate over the association between oxidative stress and mortality. Our study aims to compare head-to-head the prognostic value of different oxidative markers for all-cause mortality in hemodialysis (HD) patients.
View Article and Find Full Text PDFBetter characterization of the potential kidney transplant recipient using novel biomarkers, for example, pretransplant plasma endotrophin, will lead to improved outcome after transplantation. This mini-review will focus on current knowledge about pretransplant recipients' characteristics, biomarkers, and immunology. Clinical characteristics of recipients including age, obesity, blood pressure, comorbidities, and estimated survival scores have been introduced for prediction of recipient and allograft survival.
View Article and Find Full Text PDFDelayed graft function after kidney transplantation is common and increases morbidity and health care costs. There is evidence that endotrophin, a specific fragment of pro-collagen type VI, promotes the inflammatory response in kidney diseases. We tested the hypothesis that pretransplant endotrophin in kidney transplant recipients may be associated with the risk of delayed graft function.
View Article and Find Full Text PDFCurrently, the most effective strategy for dealing with Alzheimer's disease (AD) is delaying the onset of dementia. Severe hypoglycemia is strongly associated with dementia; however, the effects of recurrent moderate hypoglycemia (RH) on the progression of cognitive deficits in patients with diabetes with genetic susceptibility to AD remain unclear. Here, we report that insulin-controlled hyperglycemia slightly aggravated AD-type pathologies and cognitive impairment; however, RH significantly increased neuronal hyperactivity and accelerated the progression of cognitive deficits in streptozotocin-induced (STZ-induced) diabetic APP/PS1 mice.
View Article and Find Full Text PDFBackground: It is unknown whether lockdown due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may affect both clinical outcome in kidney transplant recipients and health care economics in Denmark.
Methods: We compared kidney transplant data at a tertiary university hospital before and during the lockdown period from March 13, 2020 until March 31, 2021, as well as kidney transplant data from Scandiatransplant for entire Denmark. Outcome variables included fall of plasma creatinine during the first postoperative day, and graft function three months posttransplant.
Background: Angiopoietin-2 (Ang-2) plays a pivotal role in pathological vascular remodeling and angiogenesis. Both vascular mechanisms are active in patients with end-stage renal disease (ESRD) and may contribute to the high mortality in these patients. The aim of this multicenter prospective cohort study was to investigate baseline serum Ang-2 concentrations in ESRD patients on hemodialysis (HD) for their ability to predict all-cause mortality.
View Article and Find Full Text PDFIntroduction: Viremia after renal transplantation is a major cause of morbidity and mortality and treatment opportunities are limited. Tests to determine the increased risk for viremia would be preferable.
Methods: In a prospective, single-center study, we conducted follow-up of 163 renal transplant recipients after incident living donor renal transplantation.
Diabetic nephropathy (DN) is a major complication of diabetes mellitus and a primary cause of end-stage renal failure. Clinical studies indicate that metabolic surgery improves DN; however, the mechanism remains unclear. Here, we report that Roux-en-Y Gastric Bypass (RYGB) surgery significantly blocked and reversed DN without affecting the insulin signaling pathway.
View Article and Find Full Text PDFRenal fibrosis is a hallmark of chronic kidney disease (CKD) caused by an imbalance between formation and degradation of extracellular matrix proteins. We investigated the collagen turnover profile of 81 non-dialysis CKD stage 2-5 patients by measuring peptides reflecting formation and degradation of collagen type (COL) I, III, IV, and VI. Based on the collagen turnover profile, we identified four clusters of patients.
View Article and Find Full Text PDFβ-1,4-mannosylglycoprotein 4-β-N-acetylglucosaminyltransferase (MGAT3) is a key molecule for the innate immune system. We tested the hypothesis that intronic antisense long non-coding RNA, MGAT3-AS1, can predict delayed allograft function after kidney transplantation. We prospectively assessed kidney function and MGAT3-AS1 in 129 incident deceased donor kidney transplant recipients before and after transplantation.
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