Abstract:
:Chronic kidney disease (CKD) promotes development of cardiac abnormalities and is highly prevalent in patients with heart failure, particularly in those with preserved ejection fraction. CKD is associated with endothelial dysfunction, however, whether CKD can induce impairment of endothelium-to-cardiomyocyte crosstalk leading to impairment of cardiomyocyte function is not known. The sodium-glucose co-transporter 2 inhibitor, empagliflozin, reduced cardiovascular events in diabetic patients with or without CKD, suggesting its potential as a new treatment for heart failure with preserved ejection fraction. We hypothesized that uremic serum from patients with CKD would impair endothelial control of cardiomyocyte relaxation and contraction, and that empagliflozin would protect against this effect. Using a co-culture system of human cardiac microvascular endothelial cells with adult rat ventricular cardiomyocytes to measure cardiomyocyte relaxation and contraction, we showed that serum from patients with CKD impaired endothelial enhancement of cardiomyocyte function which was rescued by empagliflozin. Exposure to uremic serum reduced human cardiac microvascular endothelial cell nitric oxide bioavailability, increased mitochondrial reactive oxygen species and 3-nitrotyrosine levels, indicating nitric oxide scavenging by reactive oxygen species. Empagliflozin attenuated uremic serum-induced generation of endothelial mitochondrial reactive oxygen species, leading to restoration of nitric oxide production and endothelial-mediated enhancement of nitric oxide levels in cardiomyocytes, an effect largely independent of sodium-hydrogen exchanger-1. Thus, empagliflozin restores the beneficial effect of cardiac microvascular endothelial cells on cardiomyocyte function by reducing mitochondrial oxidative damage, leading to reduced reactive oxygen species accumulation and increased endothelial nitric oxide bioavailability.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Juni RP,Al-Shama R,Kuster DWD,van der Velden J,Hamer HM,Vervloet MG,Eringa EC,Koolwijk P,van Hinsbergh VWMdoi
10.1016/j.kint.2020.12.013subject
Has Abstractpub_date
2020-12-22 00:00:00eissn
0085-2538issn
1523-1755pii
S0085-2538(20)31532-5pub_type
杂志文章abstract:BACKGROUND:Middle molecules such as beta2-microglobulin (beta2M) and advanced glycation end products (AGE)-modified proteins contribute to inflammation in uremia. The BetaSorb column is a new adsorptive device, which contains copolymeric beads, suitable for removal of beta2M and other middle molecules. We assessed the ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00839.x
更新日期:2003-03-01 00:00:00
abstract:BACKGROUND:It is known that inhibition of cyclooxygenase (COX) impairs the renal actions of loop diuretics. Recently, we found that cyclosporine A (CsA) inhibits renal COX-2 expression. Therefore, we examined the interferences of CsA with the renal actions of loop diuretics. METHOD:We investigated the renal effects of...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00627.x
更新日期:2004-06-01 00:00:00
abstract::Hemodynamic factors may play a role in the development of acute renal failure following administration of contrast media (CM). In this study the effect of intravenous injection of contrast media and mannitol on red blood cell velocity (VRBC) and red blood cell aggregation in renal medullary vessels was studied in 58 r...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.181
更新日期:1996-05-01 00:00:00
abstract::Chronic kidney disease (CKD) is usually associated with interstitial leukocytic cell infiltrates, which may contribute to disease progression by production of proinflammatory, proapoptotic, and profibrotic mediators. Recruiting leukocytes into the kidney involves local expression of chemotactic cytokines, that is, che...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5000053
更新日期:2006-01-01 00:00:00
abstract::The impact of early-diagnosed new-onset post-transplantation diabetes mellitus (PTDM) on cardiovascular (CV) disease is not well described. The objectives of the present prospective single-center observational study were to assess the long-term effects of early-diagnosed new-onset PTDM on major cardiac events (MCE; ca...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000116
更新日期:2006-02-01 00:00:00
abstract::In organ donation, the donor, recipient, and transplant team must all accept potential health risks to the donor and any uncertainties. To gauge these risks, we surveyed general altruism and risk-taking behaviors in 112 potential donors, 111 potential recipients, and 51 transplant professionals. Next, participants ind...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.65
更新日期:2008-05-01 00:00:00
abstract::Diabetic kidney disease is the leading cause of kidney failure. However, studies of molecular mechanisms of early kidney damage are lacking. Here we examined for possible linkage between transcriptional regulation and quantitative structural damage in early diabetic kidney disease in Pima Indians with type 2 diabetes....
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2017.08.013
更新日期:2018-02-01 00:00:00
abstract::In adults on chronic hemodialysis, achieving a hemoglobin concentration of 12g/dl and above with erythropoiesis stimulating agents leads to increased cardiovascular events and mortality, but this may not be true in children. Therefore, we conducted a retrospective cohort study of pediatric patients (under 18) from the...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.09.013
更新日期:2017-01-01 00:00:00
abstract::The presence of nitric oxide (NO) in the kidney has been implicated in the pathogenesis of human glomerulonephritis. However, the exact type of glomerular cells that express NO synthase (NOS) and the NOS isoform involved in the local production of NO has not been identified in the human diseased kidney. We examined th...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00907.x
更新日期:1998-06-01 00:00:00
abstract::The association between dietary sodium and potassium intake with the development of kidney disease remains unclear, particularly among younger individuals. Here, we determined whether dietary sodium and potassium intake are associated with incident chronic kidney disease (CKD) using data from 1,030 adults (age 23-35 i...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.02.037
更新日期:2020-07-01 00:00:00
abstract:BACKGROUND:Normalization of proteinuria and even regression of glomerulosclerosis seem to occur in progressive renal disease upon blockade of the renin-angiotensin system. Here we quantified the effect of a combination of an angiotensin converting enzyme (ACE) inhibitor and an angiotensin II (Ang II) receptor antagonis...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00526.x
更新日期:2002-09-01 00:00:00
abstract::Intestinal regulation of oxalate absorption is a complex mechanism, not exclusively reliant on the oxalate-degrading anaerobe Oxalobacter formigenes. Using metagenomics, Miller et al. were able to describe a network of bacterial taxa co-occurring with Oxalobacter formigenes in fecal samples from non-stone forming cont...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2019.03.020
更新日期:2019-07-01 00:00:00
abstract:BACKGROUND:Controversy exists regarding the possible associations between a single nucleotide polymorphism of the transcobalamin II encoding gene (TCN2 776C>G) and plasma levels of vitamin B(12), folate, or total homocysteine. METHODS:In a cross-sectional study of 732 kidney allograft recipients, patients were categor...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00592.x
更新日期:2004-05-01 00:00:00
abstract::For reasons that are not well understood, Aboriginal people with end-stage renal disease (ESRD) have lower rates of kidney transplantation. We hypothesized that distance between residence location and the closest transplant center was greater in Aboriginal dialysis patients and would partially explain the lower rate o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5001607
更新日期:2006-09-01 00:00:00
abstract::Urinary exosomes containing apical membrane and intracellular fluid are normally secreted into the urine from all nephron segments, and may carry protein markers of renal dysfunction and structural injury. We studied methods for collection, storage, and preservation of urinary exosomal proteins. We collected urine fro...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000273
更新日期:2006-04-01 00:00:00
abstract:BACKGROUND:Although renal protective effect of interrupting the inflammatory process is well established, it is still controversial if it also prevents the glomerular hemodynamic disturbances that initiate renal injury. We investigated the effects of suppressing inflammation with mycophenolate mofetil (MMF) on glomerul...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00811.x
更新日期:2003-03-01 00:00:00
abstract::Neutrophil (PMN) recruitment into the peritoneum during acute bacterial peritonitis is an important part of the host defense barrier in CAPD patients. However, the subsequent phagocytosis of bacteria may also lead to PMN degranulation and the release of lysosomal enzymes. We determined the concentration of neutrophil ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.216
更新日期:1993-07-01 00:00:00
abstract::The present study was undertaken to: (a) clarify the comparative renal potency of bolus injection of the natriuretic peptides urodilatin and ANF99-126 in the rat; (b) establish whether or not intravenous (i.v.) infusion of urodilatin (200 ng/min) combined with dopamine (UD) to maintain mean arterial pressure could imp...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.399
更新日期:1992-11-01 00:00:00
abstract:BACKGROUND:An Experimental model of proliferative glomerulonephritis induced by an antibody against Thy-1 antigen has been established. However, the pathophysiologic role and the critical epitope of Thy-1 molecule for induction of mesangial cell dysfunction remain unknown. We have reported that monoclonal antibody 1-22...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.66011.x
更新日期:2004-12-01 00:00:00
abstract:BACKGROUND:The hypothesis that angiotensin-converting enzyme (ACE) inhibitors interfere with the treatment of anemia with recombinant human erythropoietin (rHuEPO) remains controversial. To test this hypothesis, a retrospective analysis was conducted in a large group of hemodialysis patients with renal anemia. METHODS...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00028.x
更新日期:2001-11-01 00:00:00
abstract::US adults with metabolic syndrome, as defined by National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, have been shown to be at increased risk of chronic kidney disease (CKD), but there is limited information in other populations. The relationship between metabolic syndrome and CKD ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002128
更新日期:2007-04-01 00:00:00
abstract::The present study examined the effect of elevated glucose on glomerular cell membrane lipid peroxidation. Glomeruli were isolated from male Sprague-Dawley rat kidneys utilizing a standard sieving method and incubated in medium containing different concentrations of glucose at 37 degrees C for one and 48 hours. The lev...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.461
更新日期:1994-12-01 00:00:00
abstract::Kidney cancer, although relatively rare when compared to other malignancies, occurs not uncommonly in patients with renal disease and is often discovered incidentally during the initial nephrologic work-up, or by the savvy clinician who is familiar with the paraneoplastic signs. While surgical approaches are generally...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5000065
更新日期:2006-01-01 00:00:00
abstract::The recent identification of RPGRIP1L as a Joubert syndrome gene brings the total of known genes to five. Three of these are also associated with the lethal Meckel syndrome, and two with Senior-Løken syndrome; both of these disorders share Joubert syndrome phenotypes, illustrating the genetic complexity of this. ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5002577
更新日期:2007-12-01 00:00:00
abstract::Angiotensin II plays an important role in the regulation of blood pressure, body salt and fluid balance, and urine concentration. Mice with deletion of the AT(1a) receptor develop polyuria and urine concentration defects. We studied the mechanisms of these urine concentration defects by treating wild-type and AT(1a)-k...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.134
更新日期:2009-07-01 00:00:00
abstract:BACKGROUND:The "intact" parathyroid hormone (PTH) assay recognizes PTH-(1-84) as well as amino terminally truncated PTH fragments, that is, large carboxyterminal PTH fragments (C-PTH fragments). The present study investigated whether the use of the plasma PTH-(1-84)/C-PTH fragment ratio enhances the noninvasive assessm...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00949.x
更新日期:2001-10-01 00:00:00
abstract:BACKGROUND:Impaired reproductive function accompanies chronic renal insufficiency (uremia) in both the human and experimental animal. Clinical hypogonadism occurs in both genders. The present studies were designed to investigate possible anti-ovulatory effects of uremia in the female rat, a species that produces multip...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00203.x
更新日期:2000-08-01 00:00:00
abstract::Changes in tissue oxygen levels trigger molecular signaling pathways that regulate cellular proliferation and differentiation in multiple cell types. The functional role of oxygen signaling in the immune system is not well understood. Rama and colleagues demonstrate that hypoxia induces dendritic-cell maturation; thus...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.15
更新日期:2008-04-01 00:00:00
abstract::Iron is critical for cellular, organismal, and possibly universal existence. Use of iron complexes to treat human diseases is ancient and is described in detail in Ayurveda/Siddha systems of medicine. Old aphorisms from Siddha medicine ("Alavukku Minjinal Amirdhamum Nanjagum," an elixir turns poisonous when taken in e...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2016.02.035
更新日期:2016-07-01 00:00:00
abstract::Progressive renal vascular sclerosis is a key feature of chronic kidney disease (CKD). Adiponectin, an adipokine with potent anti-inflammatory and antiatherosclerotic properties, is associated with insulin resistance, type II diabetes and cardiovascular disease. In this study, we evaluated the predictive value of adip...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002191
更新日期:2007-06-01 00:00:00