Rapid Loss Of Kidney Function Research Articles

#1771 ANXA13 protects against acute kidney injury by inhibiting TGF-β/Smad3 pathway

Abstract Background and Aims Acute kidney injury (AKI) is a common clinical syndrome characterized by rapid loss of kidney function but with limited diagnostic and treatment options. Annexins (ANXA) are a superfamily of calcium-dependent and lipid-binding proteins involved in multiple intracellular and extracellular functions. As a founding member of ANXA, ANXA13 is considered the prototype of a conserved evolutionary property of the annexin superfamily and is restricted to kidney and intestinal epithelial cells. However, it is currently unclear whether ANXA13 is a key regulator of AKI. Therefore, we aimed to investigate the role of ANXA13 in AKI. Method Kidney biopsy tissues from AKI patients were collected for immunohistochemical examination and ELISA method was used to detect the concentration of ANXA13 in serum and urine. A mouse model of AKI induced by ischemia-reperfusion injury (IRI) was established to verify the role of ANXA13 in AKI. RNA sequencing was also used to explore the mechanism of ANXA13 in AKI, and this result was further confirmed using Smad3 wild-type (WT) and knockout (KO) mice. Results AKI patients had reduced serum ANXA13 levels and increased urinary ANXA13 levels compared with healthy controls. The levels of ANXA13 in both serum and urine are related to serum creatinine (Scr). In kidney tissue, ANXA13 was significantly reduced in both AKI patients and IRI-AKI mice. By overexpressing ANXA13 by specifically transferring ANXA13-expressing plasmid into IRI-AKI mice via ultrasound microbubble-mediated kidney, we found that ANXA13 reduced Scr and blood urea nitrogen (BUN) levels and renal function in IRI-AKI mice. damage. In contrast, knockdown of ANXA13 by shANXA13 plasmid significantly exacerbated renal injury. Mechanistically, we found that the protective mechanism of ANXA13 was related to the inhibition of the TGF-β/Smad3-p21 cell cycle arrest pathway, and the aggravating effect of shANXA13 was reversed in Smad3 knockout mice. In turn, activation of Smad3 also suppresses ANXA13 mRNA and protein levels in vivo and in vitro. Conclusion ANXA13 can intervene in AKI by inhibiting the TGF-β/Smad3-p21 cell cycle blocking pathway. In turn, activation of Smad3 inhibits ANXA13 expression. Therefore, ANXA13 may be a new therapeutic target for AKI.

Relevance of histopathological findings for predictive scoring of short-term treatment response to plasma exchange in severe ANCA-associated renal vasculitides.

Rapidly progressive glomerulonephritis (RPGN) is characterized by a rapid loss of kidney function, affecting both renal and overall patient survival. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis affecting multiple organ systems including the kidney, and among most frequent causes of RPGN. We here aimed to validate a recently described scoring system for short-term treatment response to therapeutic plasma exchange (PLEX) in a well-characterized and independent cohort of severe renal AAV presenting with RPGN. Furthermore, we compared this scoring with established classification systems in renal AAV including histopathological findings. We here directly compare the scoring system with retrospective data about PLEX treatment in our own clinical practice and according to current recommendations in a cohort of 53 patients with severe AAV presenting with RPGN confirmed by kidney biopsy. We here confirm that PLEX scoring is capable to identify patients at risk for short-term poor outcome in severe AAV presenting with RPGN (p<0.0001). Furthermore, multiple stepwise regression analysis revealed that the PLEX score with renal biopsy performed best to predict poor outcome in this patient population (p<0.0001). Our observations underscore the relevance of performing a kidney biopsy in this patient population that is often challenged in the setting of intensive care treatment, requirement of KRT with need for anticoagulation and bleeding risk. Therefore, validation of our observations and this recent scoring system for treatment response to PLEX in independent cohorts would be of great clinical relevance in the treatment of patients with severe AAV presenting with RPGN.

#2968 PROGNOSIS OF CRESCENTIC GLOMERULONEPHRITIS IN ADULTS

Abstract Background and Aims Crescentic glomerulonephritis (C-GN) is characterized by severe glomerular inflammation and injury that leads to crescent formation, rapid loss of kidney function and severe prognosis in absence of prompt immunosuppressive therapy. Depending on the histological findings, there are three main types of C-GN: anti-glomerular basement membrane antibody GN (anti-GBM GN), immune complex GN, and pauci-immune GN. This study aims to assess whether the kidney and vital outcome are different among the three histologic types of crescentic GN. Method This unicentric, retrospective study included seventy-six subjects [50% males, 55 (95%CI 52 to 60) years; eGFR 9.6 (95%CI 7.8-13.7) mL/min and proteinuria 1.9 (95%CI 1.5 to 2.6) g/g] that had undergone a kidney biopsy between 1st January 2008 and 31st December 2017 and had a histologic diagnosis of crescentic glomerulonephritis (crescent formation in more than 50% of the glomeruli). The subjects were followed for a mean of 47.6 (95%CI 33.5 to 61.6) months. Primary endpoints were the need of renal replacement therapy initiation (RRT) and all cause death. Kaplan-Meier method was used to evaluate kidney and patients’ survival and variables related to kidney and vital outcome were evaluated by multivariate Cox proportional hazard modelling. Patients were stratified in three groups according to the type of C-GN: pauci-immune GN (n=58 pts.), anti-GBM GN (n=9 pts.) and immune-complex GN (n=9 pts.). Results No demographic differences were found among the three groups. Except for a higher frequency of solid neoplasia in immune-complex GN group (2.7% vs 1.3% in pauci-immune GN vs. 0% in anti-GBM GN; P = .001), no other differences regarding the clinical or laboratory data were identified. Immunosuppressive treatment was very frequent, in more than 80% of subjects, regardless of the group, corticotherapy and cyclophosphamide being the most common immunosuppressive agents. During the follow-up period, 54% of subjects needed RRT and 19.2% died. The frequency of RRT initiation or death was not different among the three groups (P = .9 and P = .4). The univariate time-dependent analysis showed similar survival times among the analysed groups (log rank =0.9) (Figure 1). In the multivariate analysis, the only independent predictor of RRT was lower baseline eGFR (OR 0.49 (95%CI 0.31 to 0.78), P = .03). Time to death did not differ among groups (log rank P = .4) (Figure 2). The only independent predictor of death was higher Charlson comorbidity score (OR 56.8 (95%CI 6.3 to 512), p&amp;lt;0.001) in the Cox analysis. Conclusion In this cohort of subjects with crescentic glomerulonephritis, although limited by the low number of subjects, the kidney and vital prognosis seem to be similar indifferent of the histologic type of crescentic glomerulonephritis.

Atherosclerotic renovascular disease: a clinical practice document by the European Renal Best Practice (ERBP) board of the European Renal Association (ERA) and the Working Group Hypertension and the Kidney of the European Society of Hypertension (ESH).

Atherosclerotic renovascular disease (ARVD) is the most common type of renal artery stenosis. It represents a common health problem with clinical presentations relevant to many medical specialties and carries a high risk for future cardiovascular and renal events, as well as overall mortality. The available evidence regarding the management of ARVD is conflicting. Randomized controlled trials failed to demonstrate superiority of percutaneous transluminal renal artery angioplasty (PTRA) with or without stenting in addition to standard medical therapy compared with medical therapy alone in lowering blood pressure levels or preventing adverse renal and cardiovascular outcomes in patients with ARVD, but they carried several limitations and met important criticism. Observational studies showed that PTRA is associated with future cardiorenal benefits in patients presenting with high-risk ARVD phenotypes (i.e. flash pulmonary oedema, resistant hypertension or rapid loss of kidney function). This clinical practice document, prepared by experts from the European Renal Best Practice (ERBP) board of the European Renal Association (ERA) and from the Working Group on Hypertension and the Kidney of the European Society of Hypertension (ESH), summarizes current knowledge in epidemiology, pathophysiology and diagnostic assessment of ARVD and presents, following a systematic literature review, key evidence relevant to treatment, with an aim to support clinicians in decision making and everyday management of patients with this condition.

Identification and validation of hub genes in drug induced acute kidney injury basing on integrated transcriptomic analysis.

Drug-induced acute kidney damage (DI-AKI) is a clinical phenomenon of rapid loss of kidney function over a brief period of time as a consequence of the using of medicines. The lack of a specialized treatment and the instability of traditional kidney injury markers to detect DI-AKI frequently result in the development of chronic kidney disease. Thus, it is crucial to continue screening for DI-AKI hub genes and specific biomarkers. Differentially expressed genes (DEGs) of group iohexol, cisplatin, and vancomycin's were analyzed using Limma package, and the intersection was calculated. DEGs were then put into String database to create a network of protein-protein interactions (PPI). Ten algorithms are used in the Cytohubba plugin to find the common hub genes. Three DI-AKI models' hub gene expression was verified in vivo and in vitro using PCR and western blot. To investigate the hub gene's potential as a biomarker, protein levels of mouse serum and urine were measured by ELISA kits. The UUO, IRI and aristolochic acid I-induced nephrotoxicity (AAN) datasets in the GEO database were utilized for external data verification by WGCNA and Limma package. Finally, the Elisa kit was used to identify DI-AKI patient samples. 95 up-regulated common DEGs and 32 down-regulated common DEGs were obtained using Limma package. A PPI network with 84 nodes and 24 edges was built with confidence >0.4. Four hub genes were obtained by Algorithms of Cytohubba plugin, including TLR4, AOC3, IRF4 and TNFAIP6. Then, we discovered that the protein and mRNA levels of four hub genes were significantly changed in the DI-AKI model in vivo and in vitro. External data validation revealed that only the AAN model, which also belonged to DI-AKI model, had significant difference in these hub genes, whereas IRI and UUO did not. Finally, we found that plasma TLR4 levels were higher in patients with DI-AKI, especially in vancomycin-induced AKI. The immune system and inflammation are key factors in DI-AKI. We discovered the immunological and inflammatory-related genes TLR4, AOC3, IRF4, and TNFAIP6, which may be promising specific biomarkers and essential hub genes for the prevention and identification of DI-AKI.

Rapid Progression of Focal Segmental Glomerulosclerosis in Patients with High-Risk APOL1 Genotypes.

FSGS is a heterogeneous diagnosis with a guarded prognosis. Polymorphisms in the apolipoprotein L1 ( APOL1 ) gene are associated with developing FSGS and faster progression to kidney failure in affected patients. Better understanding the natural history of patients with FSGS and APOL1 risk alleles is essential to improve patient care and support the design and interpretation of interventional studies. The objective of this study was to evaluate the quantitative association between APOL1 and kidney disease progression and the interaction with other clinical and laboratory factors. CureGN cohort study participants with biopsy diagnosis of FSGS, regardless of self-identified race, were included. The exposure of interest was two APOL1 risk alleles (high risk) versus zero to one risk alleles (low risk). The primary outcome was eGFR slope categorized as rapid progressor (eGFR slope ≤-5 ml/min per year), intermediate progressor (slope between 0 and -5), or nonprogressor (slope ≥0). Multivariable ordinal logistic and linear regressions were used for adjusted analyses. Missing data were addressed using multiple imputation. Of 650 participants, 476 (73%) had genetic testing, among whom 87 (18%) were high risk. High-risk participants were more likely to have lower median eGFR (62 [interquartile range, 36-81] versus low-risk participants 76 ml/min per 1.73 m 2 [interquartile range, 44-106]; P <0.01). In adjusted analysis, the odds of more rapid progression of eGFR was 2.75 times higher (95% confidence interval, 1.67 to 4.53; P <0.001) in the high-risk versus low-risk groups. In patients with FSGS, high-risk APOL1 genotype is the predominant factor associated with more rapid loss of kidney function.

Клиническое наблюдение пациента с прогрессирующим снижением почечной функции после COVID-19

The article presents the results of a clinical observation of a case of acute kidney injury with an end-stage renal disease development in a patient who had had COVID-19 twice. The difficulties of the diagnostic search and further therapy are described. The characteristics of the clinical course and functional features of the patient are given. The mechanisms of the SARS-CoV-2 virus impact on the human body and their role in kidney damage are considered. This clinical case is an example of a rapid loss of kidney function with the development of end-stage renal disease against the background of COVID-19.

Innate immune response in the patients with heart disease and acute kidney injury after coronary artery bypass grafting, depending on the duration of extracorporeal circulation

Incidence of chronic diseases is increased in the 21st century due to prolonged life expectancy. Cardiovascular disease is the most common disorder worldwide, complicated with high morbidity and mortality. Upon increased prevalence of this disease, cardiac surgery has become an essential strategy for patients that do not respond to medications and other therapeutic procedures. Some potential complications in cardiac surgery affect kidneys, lung, brain over the postoperative period. Acute kidney injury (AKI) is considered a serious complication of cardiac surgery characterized by rapid loss of kidney function leading to acute increase in the serum creatinine concentration. AKI occurs in up to 30% of patients after cardiac surgery and is observed in 2% of the cases with isolated coronary artery bypass grafting (CABG). There are literature data concerning the patients with coronary artery disease after CABG in the presence of evolving atherosclerosis. Development of inflammation and dysadaptation of innate immunity was established in this work. An imbalance in the cytokine system contributes to the progression of endothelial dysfunction and may promote development of renal injury after CABG. Hypercytokinemia in AKI patients suggests involvement of innate immunity factors in the development of acute inflammatory response. The purpose of this article was to assess the innate immune response in the patients subjected to CABG with different duration of extracorporeal circulation. In the present study, 100 patients underwent CABG, all of whom were in the on-pump group. General clinical, functional, biochemical, instrumental, immunological and statistical methods were used in the work. After analyzing the data on the content of pro- and anti-inflammatory cytokines in blood serum of the patients with stage 1 and 2 AKI (KDIGO), depending on the duration of cardiopulmonary bypass surgery, we found that their dynamics corresponded to the standard pattern of changes after CABG groups and hyperproduction of pro- and anti-inflammatory cytokines in the groups with higher duration of cardiopulmonary bypass. The pathogenetic role of pro- and anti-inflammatory mediators remains unclear. We support the view that the clinical prognosis after cardiopulmonary bypass depends on the balance of pro- and anti-inflammatory cytokines.

Soluble CD89 is a critical factor for mesangial proliferation in childhood IgA nephropathy

Childhood IgA nephropathy (IgAN) includes a wide spectrum of clinical presentations, from isolated hematuria to acute nephritis with rapid loss of kidney function. In adults, IgAN is an autoimmune disease and its pathogenesis involves galactose deficient (Gd) IgA1, IgG anti-Gd-IgA1 autoantibodies and the soluble IgA Fc receptor (CD89). However, implication of such factors, notably soluble CD89, in childhood IgAN pathogenesis remains unclear. Here, we studied these biomarkers in a cohort of 67 patients with childhood IgAN and 42 pediatric controls. While Gd-IgA1 was only moderately increased in patient plasma, levels of circulating IgA complexes (soluble CD89-IgA and IgG-IgA) and free soluble CD89 were markedly increased in childhood IgAN. Soluble CD89-IgA1 complexes and free soluble CD89 correlated with proteinuria, as well as histological markers of disease activity: mesangial, endocapillary hypercellularity and cellular crescents. Soluble CD89 was found in patient's urine but not in urine from pediatric controls. Mesangial deposits of soluble CD89 were detected in biopsies from patients with childhood IgAN. Serum chromatographic fractions containing covalently linked soluble CD89-IgA1 complexes or free soluble CD89 from patients induced mesangial cell proliferation invitro in a soluble CD89-dependent manner. Recombinant soluble CD89 induced mesangial cell proliferation invitro which was inhibited by free soluble recombinant CD71 (also a mesangial IgA receptor) or mTOR blockers. Interestingly, injection of recombinant soluble CD89 induced marked glomerular proliferation and proteinuria in mice expressing human IgA1. Thus, free and IgA1-complexed soluble CD89 are key players in mesangial proliferation. Hence, our findings suggest that soluble CD89 plays an essential role in childhood IgAN pathogenesis making it a potential biomarker and therapeutic target.

Etiology &amp; Outcome of Acute kidney Injury in Intensive Care Unit Settings of a Tertiary Care Hospital

Introduction: Acute kidney injury (AKI) is defined as a rapid loss of kidney function occurring over few hours or days. In intensive care unit settings, acute kidney injury (AKI) is a very prevalent condition as most of the patients who are admitted in intensive care units are critically ill. The incidence of acute kidney injury is increasing throughout the world mainly because of aging population and co morbidities which are associated with aging. In intensive care unit settings, the incidence of AKI may reach up to 67%. Though AKI effects depend on clinical situation yet associated with high morbidity and mortality. The rationale of this study is that, as acute kidney is one of major factors contributing in mortality and morbidity of ICU patients, this study will be helpful in identifying important risk factor for development of acute kidney injury in ICU settings, leading to its early detection and thus decreasing associated morbidity and mortality. Objective: To determine the frequency of etiology and outcome of acute kidney injury in medical intensive care unit of KRL Hospital. Setting: Medical ICU, KRL Hospital, Islamabad. Duration: six months from 17th May 2017 to 17th November 2017. Study design: Descriptive case series. Material and method: In this study 118 patients were observed. After screening and application of exclusion criteria, a total of 118 patients who were fulfilling the inclusion criteria were selected as the study sample and were included in the final analysis regarding prevalence of risk factors associated with AKI and the outcome associated with AKI. AKI was further classified using acute kidney injury network (AKIN) classification system. Patient age, gender, serum creatinine, etiology and outcome in form of recovery or mortality was recorded. Results: Overall incidence of AKI in ICU settings in this study was 37.8% (n=118). Out of 118 patients who had AKI, 59.3% (n=70) were male, whereas 40.7% (n=48) were females. Most common risk factor associated with development of AKI was sepsis secondary to infectious illnesses and 39% (n=46) of the patients who developed AKI were suffering from infectious illnesses. Gastrointestinal, drugs and cardiac causes constitutes the 32.2 % (n=38), 18.6% (n=22) and 10.2% (n=12) respectively of the AKI in ICU settings. In terms of outcome, mortality rate in patients with AKI was significantly higher as compared to patients without AKI(P =&lt;0.001) and 56.8%(n=67) of the patients who had AKI died during their ICU stay as compared to 30.4%(n=59) in patients without AKI. Conclusion: Our study concludes that the frequency of etiology including infectious causes was 39%, cardiac pathology 10%, GI causes 32%, drugs was 19% and mortality was 56.8% in patients with acute kidney injury.

Etiology of acute kidney injury in intensive care unit settings

Introduction: Acute kidney injury (AKI) is defined as a rapid loss of kidney function occurring over few hours or days. In intensive care unit settings, acute kidney injury (AKI) is a very prevalent condition as most of the patients who are admitted in intensive care units are critically ill. The incidence of acute kidney injury is increasing throughout the world mainly because of aging population and comorbidities which are associated with aging. In intensive care unit settings, the incidence of AKI may reach up to 67%. Though AKI effects depend on clinical situation yet associated with high morbidity and mortality. Objective: To determine the frequency of etiology of acute kidney injury in medical intensive care unit of KRL Hospital. Setting: Medical ICU, KRL Hospital, Islamabad. Duration: six months from 17th May 2017 to 17th November 2017. Study design: Descriptive case series. Material and method: In this study 118 patients were observed. After screening and application of exclusion criteria, a total of 118 patients who were fulfilling the inclusion criteria were selected as the study sample and were included in the final analysis regarding prevalence of risk factors associated with AKI. AKI was further classified using acute kidney injury network (AKIN) classification system. Patient age, gender, serum creatinine, etiology and outcome in form of recovery or mortality was recorded on specific proforma. Results: Overall incidence of AKI in ICU settings in this study was 37.8%(n=118) .Out of 118 patients who had AKI, 59.3%(n=70) were male , whereas 40.7% (n=48) were females. Most common risk factor associated with development of AKI was sepsis secondary to infectious illnesses and 39% (n=46) of the patients who developed AKI were suffering from infectious illnesses. Gastrointestinal, drugs and cardiac causes constitutes the 32.2% (n=38), 18.6% (n=22) and 10.2% (n=12) respectively of the AKI in ICU settings. Conclusion: Our study concludes that the frequency of etiology including infectious causes was 39%, cardiac pathology 10%, GI causes 32%, drugs was 19%.

Urinary excretion of epidermal growth factor and rapid loss of kidney function.

Lower urinary excretion of the kidney tubule-specific biomarker epidermal growth factor (uEGF) is associated with increased risk of renal function [glomerular filtration rate (GFR)] loss in diabetes and in patients with established chronic kidney disease (CKD). We investigated whether uEGF is associated with rapid GFR decline or incident CKD in the general population. Subjects without CKD or diabetes were recruited from the general population in Tromso, Norway [Renal Iohexol Clearance Survey (RENIS); N = 1249] and Groningen, the Netherlands [Prevention of REnal and Vascular END-stage disease (PREVEND); N = 4534], with a median follow-up of 5.6 and 7.4 years, respectively. GFR was measured by iohexol clearance in the RENIS and estimated using the CKD Epidemiology Collaboration creatinine-cystatin C equation in the PREVEND study. Rapid GFR decline was defined as an annual GFR loss >3.0 mL/min/1.73 m2 and in sensitivity analyses as subjects with the 10% steepest GFR slope within each cohort. Lower baseline uEGF excretion was associated with rapid GFR loss in both cohorts {RENIS, odds ratio [OR] per 1 μg/mmol lower uEGF 1.42 [95% confidence interval (CI) 1.06-1.91], P = 0.02; PREVEND, OR 1.29 [95% CI 1.10-1.53], P < 0.01}, adjusted for baseline GFR, albumin:creatinine ratio and conventional CKD risk factors. Similar results were obtained using the outcome of the 10% steepest GFR slope in each cohort. Lower uEGF levels were associated with incident CKD in the combined analysis of both cohorts. Lower uEGF levels are associated with increased risk of rapid GFR loss and incident CKD in the general population. This finding, together with previous findings in CKD and high-risk populations, supports that uEGF may serve as a broadly applicable biomarker representing the tubular component of the current glomerulus-centric clinical risk assessment system.

American Indian chronic Renal insufficiency cohort study (AI-CRIC study)

BackgroundChronic kidney disease (CKD) is an increasing epidemic globally that is associated with adverse health outcomes including end stage kidney disease (ESKD), cardiovascular disease (CVD), and death. American Indians (AIs) have a higher prevalence of CKD than most other racial/ethnic groups, due in part to a high prevalence of type 2 diabetes. Other genetic and environmental factors not yet identified may also contribute to the disproportionate burden of CKD in AIs.MethodWe will establish 3 clinical centers to recruit AIs from the Southwest United States (US) to expand the Chronic Renal Insufficiency Cohort (CRIC) study. We will follow the current CRIC protocol for kidney and cardiovascular measures and outcomes, which include ambulatory monitoring of kidney function and the use of mobile health technologies for CVD sub-phenotyping, and compare the outcomes in AIs with those in other racial/ethnic groups in CRIC.DiscussionAI-CRIC will identify the role of various risk factors for rapid loss of kidney function among AIs of the Southwest US. In addition, to better understand the natural history of CKD and CVD in this high-risk population, we will identify unique risk factors for CKD and CVD progression in AIs. We will also compare event rates and risk factors for kidney and cardiovascular events in AIs with the other populations represented in CRIC.

Novel 3D analysis using optical tissue clearing documents the evolution of murine rapidly progressive glomerulonephritis

Recent developments in optical tissue clearing have been difficult to apply for the morphometric analysis of organs with high cellular content and small functional structures, such as the kidney. Here, we establish combinations of genetic and immuno-labelling for single cell identification, tissue clearing and subsequent de-clarification for histoimmunopathology and transmission electron microscopy. Using advanced light microscopy and computational analyses, we investigated a murine model of crescentic nephritis, an inflammatory kidney disease typified by immune-mediated damage to glomeruli leading to the formation of hypercellular lesions and the rapid loss of kidney function induced by nephrotoxic serum. Results show a graded susceptibility of the glomeruli, significant podocyte loss and capillary injury. These effects are associated with activation of parietal epithelial cells and formation of glomerular lesions that may evolve and obstruct the kidney tubule, thereby explaining the loss of kidney function. Thus, our work provides new high-throughput endpoints for the analysis of complex tissues with single-cell resolution.

Lavender oil (Lavandula angustifolia) attenuates renal ischemia/reperfusion injury in rats through suppression of inflammation, oxidative stress and apoptosis

Renal ischemia/reperfusion (I/R) injury following kidney transplantation has been found to be a great clinical problem owing to initiation of acute inflammatory responses and subsequently rapid loss of kidney function. It is well known that lavender oil exhibits an extensive spectrum of pharmacological and biochemical activities. The purpose of this study was to clarify molecular targets of lavender in treatment of this disease.Male Wistar rats weighing 200–250 g were divided into three major groups: sham, I/R, and I/R + different doses of lavender oil (L1:50 mg/kg, L2: 100 mg/kg, and L3: 200 mg/kg). A rat model of renal I/R (45 min ischemia and 24 h reperfusion) was created and lavender was administrated at 1 h after the beginning of reperfusion (i.p). Activities of antioxidant enzymes such as SOD, GPX, and CAT, and lipid peroxidation were evaluated. The expression of inflammatory cytokines such as TNFα, IL1β, and IL10 was determined by IHC and ELISA assay. Apoptosis activity and tissue damage were evaluated by TUNEL and H & E staining, respectively.Our results showed that lavender oil markedly restored activities of antioxidant enzymes and reduced lipid peroxidation (P < 0.05). Lavender significantly decreased levels of TNFα and IL1β and increased level of IL10 in a dose-dependent manner (P < 0.05). Lavender reduced TUNEL positive cells in a dose-dependent manner. However, lavender reduced damage to peritubular capillaries and contributed to preservation of normal morphology of renal cells.In sum, our findings establish a fundamental foundation for future drug industry to decrease the rates of rejection in kidney transplant patients.

The role of sphingolipids in acute kidney injury.

Acute kidney injury (AKI) is most simply defined as the rapid loss of kidney function in a matter of hours to days. AKI can manifest in a number of ways including pre-renal, post-renal, or intrinsic AKI. During acute kidney injury, multiple pathogenic processes are activated including inflammation, cell death, and the generation of reactive oxygen species, just to name a few. Sphingolipids are known to play a role in a number of the pathogenic pathways involved in the pathogenesis of many types of AKI, which suggests a role for sphingolipids in AKI. This short review will discuss the evidence for a role for sphingolipids in AKI.

Association of Chronic Insomnia With Mortality and Adverse Renal Outcomes

ObjectiveTo examine whether chronic insomnia is associated with an increased risk of adverse renal outcomes and all-cause mortality. Patients and MethodsWe examined associations of chronic insomnia (defined as the presence of both International Classification of Diseases, Ninth Revision codes 307.42, 307.49, and 780.52 and long-term use of insomnia medications) with adverse renal outcomes (end-stage renal disease, incidence of estimated glomerular filtration rate [eGFR] ≤45 mL/min per 1.73 m2, and eGFR slopes <−3.0 mL/min per 1.73 m2 per year) and all-cause mortality in a national cohort of 1,639,090 US veterans by using Cox proportional hazards and logistic regression models with multivariable adjustments. ResultsA total of 36,741 patients (2.24%) had chronic insomnia; 32,985 (89.8%) were male and 28,090 (76.5%) were white, with a mean baseline eGFR of 84.1±16.4 mL/min per 1.73 m2. Chronic insomnia was associated with a significantly higher risk of eGFR 45 mL/min per 1.73 m2 or less (multivariable-adjusted hazard ratio [HR], 1.39; 95% CI, 1.34-1.44; P<.001), and rapid loss of kidney function (odds ratio, 1.07; 95% CI, 1.03-1.12; P=.002), but not end-stage renal disease (HR, 1.25; 95% CI, 0.81-1.93; P=.32). Chronic insomnia was not associated with a higher risk of all-cause mortality (HR, 1.00; 95% CI, 0.97-1.03; P=.99). ConclusionChronic insomnia is associated with a higher risk of development and progression of chronic kidney disease, but not ESRD. Further studies are needed to establish the underlying mechanisms of action and to determine whether treatment of insomnia could be beneficial to prevent deteriorating kidney function.

PYCARD Gene Plays a Key Role in Rapidly Progressive Glomerulonephritis: Results of a Weighted Gene Co-Expression Network Analysis

Background: Rapidly progressive glomerulonephritis (RPGN) is caused by various diseases process, thereby resulting in extensive crescent formation, which could lead to a rapid loss of kidney function. The molecular pathogenesis of RPGN remains largely unknown and requires clarification. The weighted gene co-expression network analysis (WGCNA) is a powerful bioinformatics tool to identify meaningful molecules in diseases. Methods: The dataset of GSE104948, which contains 22 RPGN and 18 normal samples, was obtained from Gene Expression Omnibus database. After data pre-processing, the WGCNA was performed to successfully cluster several significant modules. The most significant module was selected for further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Visualization of network and screening of hub genes were performed by using Cytoscape software. Results: A total of 11 modules were clustered by WGCNA, and the most significant module-turquoise module was selected. As discovered via GO enrichment and KEGG pathway analysis, the turquoise module was mainly associated with neutrophil activation and degranulation. After visualization and calculation for the network, the PYCARD gene has higher relationship score in 2 clusters, namely, neutrophil activation and degranulation. In accordance with the literature review, the hub gene could be closely related to the inflammation response and could act as the potential therapeutic targets in RPGN. Conclusions: WGCNA in RPGN expression profiling was used for the first time in this paper. A novel hub gene closely associated with RPGN was screened out, thereby providing the brand-new molecular candidate for RPGN.

Risk factors for decline in renal function among young adults with type 1 diabetes

AimsTo investigate risk factors for declining renal function among subjects with type-1-diabetes. MethodsObservational study based on data from the diabetes registry DPV. 4424 type-1-diabetes subjects aged ≥18 years, age at onset <18 years were identified. Modification of Diet in Renal Disease (MDRD) equation was used to estimate glomerular filtration rate (eGFR). Annual rate of renal decline was estimated for each patient using hierarchic linear regression models. Additional regression models were fitted to adjust for covariates. ResultsMedian age was 26 [Q1; Q3: 21; 39] years. Annual decline of renal function was −1.22 (95% CI: −1.50; −0.94) ml/min/1.73 m2. At baseline, higher eGFR was related to more rapid decline compared to impaired or reduced eGFR (GFR ≥ 90: −2.06 (−2.35; −1.76), 60 ≤ GFR < 90: 0.45 (0.08; 0.81), GFR < 60: 0.52 (−0.24; 1.29) ml/min/1.73 m2, p < 0.01). During follow-up, the highest decline was associated with reduced renal function, whereas the lowest decline was related to normal kidney function (p < 0.01). Poor metabolic control (p = 0.04), hypertension (p < 0.01) and albuminuria (p = 0.03) were associated with more rapid loss of kidney function. No difference was observed among insulin regimen. ConclusionAmong this large type-1-diabetes cohort, more rapid loss of kidney function was related to higher baseline eGFR, log-term worse metabolic control and diabetic comorbidities.

Serum Calcitriol Concentrations and Kidney Function Decline, Heart Failure, and Mortality in Elderly Community-Living Adults: The Health, Aging, and Body Composition Study

Lower 25-hydroxyvitamin D concentrations have been associated with risk for kidney function decline, heart failure, and mortality. However, 25-hydroxyvitamin D requires conversion to its active metabolite, calcitriol, for most biological effects. The associations of calcitriol concentrations with clinical events have not been well explored. Case-cohort study. Well-functioning community-living older adults aged 70 to 79 years at inception who participated in the Health, Aging, and Body Composition (Health ABC) Study. Serum calcitriol measured using positive ion electrospray ionization-tandem mass spectrometry. Major kidney function decline (≥30% decline in estimated glomerular filtration rate from baseline), incident heart failure (HF), and all-cause mortality during 10 years of follow-up. Baseline calcitriol concentrations were measured in a random subcohort of 479 participants and also in cases with major kidney function decline [n=397]) and incident HF (n=207) during 10 years of follow-up. Associations of serum calcitriol concentrations with these end points were evaluated using weighted Cox regression to account for the case-cohort design, while associations with mortality were assessed in the subcohort alone using unweighted Cox regression. During 8.6 years of mean follow-up, 212 (44%) subcohort participants died. In fully adjusted models, each 1-standard deviation lower calcitriol concentration was associated with 30% higher risk for major kidney function decline (95% CI, 1.03-1.65; P=0.03). Calcitriol was not significantly associated with incident HF (HR, 1.16; 95% CI, 0.94-1.47) or mortality (HR, 1.01; 95% CI, 0.81-1.26). We observed no significant interactions between calcitriol concentrations and chronic kidney disease status, baseline intact parathyroid or fibroblast factor 23 concentrations. Observational study design, calcitriol measurements at a single time point, selective study population of older adults only of white or black race. Lower calcitriol concentrations are independently associated with kidney function decline in community-living older adults. Future studies will be needed to clarify whether theseassociations reflect lower calcitriol concentrations resulting from abnormal kidney tubule dysfunction or direct mechanisms relating lower calcitriol concentrations to more rapid loss of kidney function.