scholarly journals Genetic Deletion of NOD1 Prevents Cardiac Ca2+ Mishandling Induced by Experimental Chronic Kidney Disease

2020 ◽  
Vol 21 (22) ◽  
pp. 8868
Author(s):  
Marta Gil-Fernández ◽  
José Alberto Navarro-García ◽  
Almudena Val-Blasco ◽  
Laura González-Lafuente ◽  
José Carlos Martínez ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Innate Immune ◽  
Cardiac Complications ◽  
Wild Type ◽  
Significant Amelioration ◽  
Genetic Deletion ◽  
Kidney Impairment ◽  
Kinetics Of ◽  
Oligomerization Domain

Risk of cardiovascular disease (CVD) increases considerably as renal function declines in chronic kidney disease (CKD). Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) has emerged as a novel innate immune receptor involved in both CVD and CKD. Following activation, NOD1 undergoes a conformational change that allows the activation of the receptor-interacting serine/threonine protein kinase 2 (RIP2), promoting an inflammatory response. We evaluated whether the genetic deficiency of Nod1 or Rip2 in mice could prevent cardiac Ca2+ mishandling induced by sixth nephrectomy (Nx), a model of CKD. We examined intracellular Ca2+ dynamics in cardiomyocytes from Wild-type (Wt), Nod1−/− and Rip2−/− sham-operated or nephrectomized mice. Compared with Wt cardiomyocytes, Wt-Nx cells showed an impairment in the properties and kinetics of the intracellular Ca2+ transients, a reduction in both cell shortening and sarcoplasmic reticulum Ca2+ load, together with an increase in diastolic Ca2+ leak. Cardiomyocytes from Nod1−/−-Nx and Rip2−/−-Nx mice showed a significant amelioration in Ca2+ mishandling without modifying the kidney impairment induced by Nx. In conclusion, Nod1 and Rip2 deficiency prevents the intracellular Ca2+ mishandling induced by experimental CKD, unveiling new innate immune targets for the development of innovative therapeutic strategies to reduce cardiac complications in patients with CKD.

scholarly journals Altered Emotional Phenotypes in Chronic Kidney Disease Following 5/6 Nephrectomy

2021 ◽  
Vol 11 (7) ◽  
pp. 882
Author(s):  
Yeon Hee Yu ◽  
Seong-Wook Kim ◽  
Dae-Kyoon Park ◽  
Ho-Yeon Song ◽  
Duk-Soo Kim ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Local Field ◽  
Smooth Muscle Actin ◽  
Local Field Potentials ◽  
Renal Tissue ◽  
Field Potentials ◽  
Wild Type ◽  
Sprague Dawley ◽  
Rat Models

Increased prevalence of chronic kidney disease (CKD) and neurological disorders including cerebrovascular disease, cognitive impairment, peripheral neuropathy, and dysfunction of central nervous system have been reported during the natural history of CKD. Psychological distress and depression are serious concerns in patients with CKD. However, the relevance of CKD due to decline in renal function and the pathophysiology of emotional deterioration is not clear. Male Sprague Dawley rats were divided into three groups: sham control, 5/6 nephrectomy at 4 weeks, and 5/6 nephrectomy at 10 weeks. Behavior tests, local field potentials, and histology and laboratory tests were conducted and investigated. We provided direct evidence showing that CKD rat models exhibited anxiogenic behaviors and depression-like phenotypes, along with altered hippocampal neural oscillations at 1–12 Hz. We generated CKD rat models by performing 5/6 nephrectomy, and identified higher level of serum creatinine and blood urea nitrogen (BUN) in CKD rats than in wild-type, depending on time. In addition, the level of α-smooth muscle actin (α-SMA) and collagen I for renal tissue was markedly elevated, with worsening fibrosis due to renal failures. The level of anxiety and depression-like behaviors increased in the 10-week CKD rat models compared with the 4-week rat models. In the recording of local field potentials, the power of delta (1–4 Hz), theta (4–7 Hz), and alpha rhythm (7–12 Hz) was significantly increased in the hippocampus of CKD rats compared with wild-type rats. Together, our findings indicated that anxiogenic behaviors and depression can be induced by CKD, and these abnormal symptoms can be worsened as the onset of CKD was prolonged. In conclusion, our results show that the hippocampus is vulnerable to uremia.

scholarly journals Cellular Mechanisms of Tissue Fibrosis. 3. Novel mechanisms of kidney fibrosis

2013 ◽  
Vol 304 (7) ◽  
pp. C591-C603 ◽  
Author(s):  
Gabriela Campanholle ◽  
Giovanni Ligresti ◽  
Sina A. Gharib ◽  
Jeremy S. Duffield
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Interstitial Fibrosis ◽  
Kidney Injury ◽  
Innate Immune ◽  
Cellular Mechanisms ◽  
Tubular Atrophy ◽  
Kidney Fibrosis ◽  
Capillary Rarefaction ◽  
Peritubular Capillaries

Chronic kidney disease, defined as loss of kidney function for more than three months, is characterized pathologically by glomerulosclerosis, interstitial fibrosis, tubular atrophy, peritubular capillary rarefaction, and inflammation. Recent studies have identified a previously poorly appreciated, yet extensive population of mesenchymal cells, called either pericytes when attached to peritubular capillaries or resident fibroblasts when embedded in matrix, as the progenitors of scar-forming cells known as myofibroblasts. In response to sustained kidney injury, pericytes detach from the vasculature and differentiate into myofibroblasts, a process not only causing fibrosis, but also directly contributing to capillary rarefaction and inflammation. The interrelationship of these three detrimental processes makes myofibroblasts and their pericyte progenitors an attractive target in chronic kidney disease. In this review, we describe current understanding of the mechanisms of pericyte-to-myofibroblast differentiation during chronic kidney disease, draw parallels with disease processes in the glomerulus, and highlight promising new therapeutic strategies that target pericytes or myofibroblasts. In addition, we describe the critical paracrine roles of epithelial, endothelial, and innate immune cells in the fibrogenic process.

scholarly journals Kinetics of Serum Carnitine Fractions in Patients With Chronic Kidney Disease Not on Dialysis

2020 ◽  
Author(s):  
JUNKO YANO ◽  
SAKUYA ITO ◽  
GOH KODAMA ◽  
YOSUKE NAKAYAMA ◽  
YUSUKE KAIDA ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kinetics Of

scholarly journals Atrial Fibrillation and Chronic Kidney Disease—A Risky Combination for Post-Contrast Acute Kidney Injury

2021 ◽  
Vol 10 (18) ◽  
pp. 4140
Author(s):  
Łukasz Kuźma ◽  
Anna Tomaszuk-Kazberuk ◽  
Anna Kurasz ◽  
Małgorzata Zalewska-Adamiec ◽  
Hanna Bachórzewska-Gajewska ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Coronary Angiography ◽  
Kidney Injury ◽  
Post Contrast ◽  
Acute Kidney Disease ◽  
Patients At Risk ◽  
Kidney Impairment

Atrial fibrillation (AF) symptoms may mimic coronary artery disease (CAD) which reflects the difficulties in qualifying AF patients for invasive diagnostics. A substantial number of coronary angiographies may be unnecessary or even put patients at risk of post-contrast acute kidney injury (PC-AKI), especially patients with chronic kidney disease (CKD). We aimed to investigate the hypothesis indicating higher prevalence of PC-AKI in patients with AF scheduled for coronary angiography. The study population comprised of 8026 patients referred for elective coronarography including 1621 with AF. In the comparison of prevalence of PC-AKI in distinguished groups we can see that kidney impairment was twice more frequent in patients with AF in both groups with CKD (CKD (+)/AF (+) 6.24% vs. CKD (+)/AF (−) 3.04%) and without CKD (CKD (−)/AF (+) 2.32% vs. CKD (−)/AF (−) 1.22%). In our study, post-contrast acute kidney disease is twice more frequent in patients with AF, especially in subgroup with chronic kidney disease scheduled for coronary angiography. Additionally, having in mind results of previous studies stating that AF is associated with non-obstructive coronary lesions on angiography, patients with AF and CKD may be unnecessarily exposed to contrast agent and possible complications.

Iron Localization and Infectious Disease in Chronic Kidney Disease Patients

2016 ◽  
Vol 43 (4) ◽  
pp. 237-244 ◽  
Author(s):  
Takeshi Nakanishi ◽  
Takahiro Kuragano ◽  
Masayoshi Nanami ◽  
Yukiko Hasuike
Keyword(s):  
Infectious Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Iron Metabolism ◽  
Innate Immune ◽  
Intracellular Growth ◽  
Iron Administration ◽  
Lower Infection ◽  
Lower Infection Rate

For patients on dialysis, infection is the second leading cause of mortality. Iron metabolism should be considered in the pathogenesis of infectious disease, as high local iron concentrations favor the growth of many microbes. This review is intended to provide information regarding iron metabolism and infection in chronic kidney disease (CKD) patients. There are 2 reasons these patients may be vulnerable to infection: (1) the excessive iron administered to treat renal anemia could be associated with impairments of the host's innate immune response, (2) CKD-associated inflammation could cause dysregulated iron metabolism. Pathogenic microorganisms can be categorized as extracellular or intracellular pathogens. The proliferation site may determine the degree of virulence. In cases of mainly extracellular microbial growth, the host's strategy of sequestering iron in cells may efficiently inhibit proliferation. However, the same strategy may favor the intracellular growth of microorganisms. The administration of excessive amounts of iron may modify iron localization by an increase in the hepcidin concentration. We conclude that there is a need for large multicenter randomized controlled trials to evaluate the long-term safety of different iron administration patterns that allow for a lower infection rate while still producing efficient erythropoiesis in CKD patients.

Myeloperoxidase deficiency ameliorates progression of chronic kidney disease in mice

2014 ◽  
Vol 307 (4) ◽  
pp. F407-F417 ◽  
Author(s):  
Alexander Lehners ◽  
Sascha Lange ◽  
Gianina Niemann ◽  
Alva Rosendahl ◽  
Catherine Meyer-Schwesinger ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Matrix Metalloproteinase ◽  
Collagen Type ◽  
Matrix Metalloproteinase 2 ◽  
Marker Genes ◽  
Wild Type ◽  
Renal Ablation ◽  
The Impact ◽  
Deficient Mice

Myeloperoxidase (MPO) is an enzyme expressed in neutrophils and monocytes/macrophages. Beside its well-defined role in innate immune defence, it may also be responsible for tissue damage. To identify the role of MPO in the progression of chronic kidney disease (CKD), we investigated CKD in a model of renal ablation in MPO knockout and wild-type mice. CKD was induced by 5/6 nephrectomy. Mice were followed for 10 wk to evaluate the impact of MPO deficiency on renal morbidity. Renal ablation induced CKD in wild-type mice with increased plasma levels of MPO compared with controls. No difference was found between MPO-deficient and wild-type mice regarding albuminuria 1 wk after renal ablation, indicating similar acute responses to renal ablation. Over the next 10 wk, however, MPO-deficient mice developed significantly less albuminuria and glomerular injury than wild-type mice. This was accompanied by a significantly lower renal mRNA expression of the fibrosis marker genes plasminogen activator inhibitor-I, collagen type III, and collagen type IV as well as matrix metalloproteinase-2 and matrix metalloproteinase-9. MPO-deficient mice also developed less renal inflammation after renal ablation, as indicated by a lower infiltration of CD3-positive T cells and F4/80-positive monocytes/macrophages compared with wild-type mice. In vitro chemotaxis of monocyte/macrophages isolated from MPO-deficient mice was impaired compared with wild-type mice. No significant differences were observed for mortality and blood pressure after renal ablation. In conclusion, these results demonstrate that MPO deficiency ameliorates renal injury in the renal ablation model of CKD in mice.

44 ONGOING KIDNEY IMPAIRMENT IN JAPANESE PATIENTS WITH PRIMARY ALDOSTERONISM: PREDICTORS OF NEW-ONSET CHRONIC KIDNEY DISEASE AFTER ADRENALECTOMY

2012 ◽  
Vol 187 (4S) ◽  
Author(s):  
Takanobu Utsumi ◽  
Atsushi Okato ◽  
Takeshi Namekawa ◽  
Tomokazu Sazuka ◽  
Mitsuru Yanagisawa ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Primary Aldosteronism ◽  
Japanese Patients ◽  
Kidney Impairment ◽  
New Onset

scholarly journals RIP2 plays a role in cardiac Ca2+ mishandling prompted by chronic kidney disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Gil-Fernandez ◽  
J.A Navarro-Garcia ◽  
A Val-Blasco ◽  
L Gonzalez-Lafuente ◽  
J.C Martinez ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cardiac Dysfunction ◽  
Fibroblast Growth Factor 23 ◽  
Funding Source ◽  
Mice Model ◽  
Health Institute ◽  
Major Player ◽  
Genetic Deletion ◽  
Carlos Iii

Abstract Background Chronic kidney disease (CKD) is a multifaceted disease that contributes to cardiac dysfunction. However, the mechanisms underlying the complex relationship between CKD and cardiac impairment remains almost completely unknown. Inflammation is a major player in both CKD and cardiovascular disease (CVD) and, in this context, nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is a newly recognized innate immune receptor involved in both CKD and CVD independently. NOD1 activation is due to the recruitment of the receptor-interacting-serine/threonine-protein kinase 2 (RIP2), which induce NOD1 oligomerization and promotes the inflammatory response, being RIP2 a key partner in the NOD1 activation. Unpublished data from our group has demonstrated that genetic deletion of NOD1 prevents Ca2+ mishandling associated to CKD, next step will be to determine whether the absence of its specific adaptor; RIP2 can also mediate these effects. Purpose The main aim of this study was to determine whether NOD1-RIP2 axis impairs cardiac dysfunction and Ca2+ mishandling prompted by CKD induced by 5/6 nephrectomy (5/6Nx) in a mice model. Methods and results We have analysed intracellular Ca2+ handling in cardiomyocytes obtained from Wild type (Wt), Nod1−/− and Rip2−/− sham operated or nephrectomised mice. Compared with Wt-5/6Nx, cardiomyocytes obtained from Nod1−/−5/6Nx and Rip2−/−5/6Nx mice showed a significant improvement of Ca2+ mishandling, mainly by preventing: i) the reduction in [Ca2+]i transients amplitude; ii) the rise in their decay time; and iii) the lower cell contraction. The lack of NOD1 and RIP2 also prevents the reduced sarcoplasmic reticulum (SR) Ca2+ load and the augmented diastolic Ca2+ leak induced by 5/6Nx. Furthermore, the increased diastolic Ca2+ leak (Ca2+ sparks, spontaneous [Ca2+]i transients and waves) induced by 5/6Nx were also significantly prevented in absence of NOD1 and RIP2. Genetic deletion of NOD1 or RIP2 did not induces any improvement of several markers associated with renal dysfunction (urea, phosphate or fibroblast growth factor-23). Conclusions Our results confirmed that the absence of both NOD1 and RIP2 prevents the intracellular cardiac Ca2+ mishandling in experimental CKD. NOD1 and RIP2 emerge as novel targets for the development of innovative therapeutic strategies for the cardiac remodelling in CKD subjects. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was supported by Spanish ISCIII (PI17/01093 and PI17/01344), Fondo Europeo de Desarrollo Regional (FEDER), FSE, and CIBER-CV, a network funded by ISCIII. MF-V is Miguel Servet II researcher of ISCIII (MSII16/00047 Carlos III Health Institute). GR-H is Miguel Servet I researcher of ISCIII (CP15/00129 Carlos III Health Institute). MT is a PhD student funded by the FPU program of the Spanish Ministry of Science, Innovation and Universities (FPU17/06135).

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