P0123THE IMPORTANCE OF PPAR-ALPHA IN AKI TO CKD TRANSITION IN NEPHROPATHY INDUCED BY FOLIC ACID

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Gabriel Estrela ◽  
Adriano Arruda ◽  
Leandro Freitas-Lima ◽  
Jonatan Barrera-Chimal ◽  
Ronaldo Araujo
Keyword(s):  
Folic Acid ◽  
Chronic Phase ◽  
Kidney Injury ◽  
Tnf Alpha ◽  
Renal Diseases ◽  
Tubular Injury ◽  
Ppar Alpha ◽  
Beneficial Effects ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background and Aims PPAR-alpha is a nuclear receptor which plays major role in the regulation of lipid metabolism, activation of PPAR-alpha has been shown to have beneficial effects in renal diseases. Acute kidney injury (AKI), even if followed by renal recovery, is a risk factor for the future development of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Our main objective was to determine the importance of PPAR-alpha in AKI to CKD transition in folic acid induced nephropathy. Method Male C57/Bl6 and PPARKO (C57Bl6 background) mice were divided in 4 groups, Control, Folic Acid, Gemfibrozil + Folic Acid and PPARKO + Folic Acid. Animals has been treated with single dose of Folic Acid (250mg/kg i.p) and Gemfibrozil (150mg/kg gavage) euthanized after 48 hours for AKI assessment and 28 days for CKD. Renal parameters, histology, real time PCR were performed to investigate renal injury, inflammation and fibrosis. Results After 48 hours of folic acid inducing AKI, PPARKO mice showed decreased urea levels (Folic Acid: 178,9±25,2 PPARKO: 92,4±15,5), less tubular injury (Folic Acid: 0,61±0,05 PPARKO: 0,21±0,03), lower mRNA expression of NGAL (Folic Acid; 32,2±7,67 PPARKO 3,74±1,71), KIM-1 (Folic Acid: 671,8±170,2 PPARKO: 43,4±29,7) and TNF-alpha (Folic Acid: 2,81±0,58 PPARKO: 0,67±0,14), while PPAR-alpha activation with gemfibrozil showed to have no effects in AKI. After 28 days of folic acid inducing CKD. PPARKO showed same levels of injury than folic acid alone treated mice, however PPAR-alpha activation with gemfibrozil decreased urea levels (Folic Acid: 79,2±3,2 Gemfibrozil: 46,1±3,8), showed less tubulointerstitial fibrosis (Folic Acid: 0,60±0,05 Gemfibrozil: 0,18±0,02) and lower urine protein/creatinine ratio (Folic Acid: 5,48±0,58 Gemfibrozil: 2,53±0,12), Conclusion PPAR-alpha deletion protects against AKI induced by folic acid but did not showed protection in chronic phase, in the other hand ppar-alpha activation with gemfibrozil did not protect in AKI but show to be effective in CKD.

Renal medicine

2021 ◽  
pp. 353-382
Author(s):  
Gopesh K. Modi ◽  
Vivekanand Jha
Keyword(s):  
Kidney Disease ◽  
Renal Disease ◽  
Rapidly Progressive Glomerulonephritis ◽  
Kidney Injury ◽  
Renal Stones ◽  
Renal Diseases ◽  
Acute Glomerulonephritis ◽  
Glomerular Diseases ◽  
Stage Renal Disease ◽  
End Stage

Assessing renal function, Urinalysis, Proteinuria, Hematuria, Chyluria, Imaging in renal disease, Kidney biopsy, Acute Kidney Injury (AKI), Chronic Kidney Disease (CKD), Diabetic Nephropathy, End Stage Renal Disease and Dialysis, Kidney Transplantation, Glomerular diseases, Acute glomerulonephritis, Urinary schistosomiasis (bilharzia), Infections and Kidney Disease, Rapidly Progressive glomerulonephritis, Tubulointerstitial Disease, Urinary Tract Infection, Vesico-ureteric reflux, Renal Stones, Renal Disease in Pregnancy, Renal Artery Stenosis, Renal Mass, Inherited Renal Diseases

P0990RENINAAV DOSE-DEPENDENTLY EXACERBATE ALBUMINURIA AND GLOMERULOSCLEROSIS, AND REDUCE GFR IN FEMALE UNINEPHRECTOMIZED DB/DB MICE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Mette Viberg Østergaard ◽  
Rune Ida ◽  
Annemarie Aarup Pedersen ◽  
Thomas Secher ◽  
Frederikke Emilie Sembach ◽  
...  
Keyword(s):  
Gene Expression ◽  
Kidney Injury ◽  
Negative Control ◽  
Tubular Injury ◽  
Spot Urine ◽  
Recent Emergence ◽  
Induced Hypertension ◽  
Stage Renal Disease ◽  
End Stage ◽  
Diabetes Patients

Abstract Background and Aims Diabetic nephropathy (DN) is a long-term complication that occurs in ∼40% of diabetes patients and is a leading cause of end-stage renal disease. Despite recent emergence of SGLT2 inhibitors and GLP-1 receptor agonists for nephroprotection in diabetes patients, drug discovery has been halted by the lack of reliable rodent models exhibiting features of human DN. In a newly established mouse model of progressive DN, we investigate the effects of hypertension on kidney injury. Method Female db/db mice were uninephrectomized (UNx) at 8 weeks of age and injected i.v. with a Renin adeno-associated virus (AAV) construct at different doses to induce hypertension, while a LacZAAV construct was used as negative control. db/+ mice served as healthy controls. Hypertension was measured by tail cuff and glomerular filtration rate (GFR) transcutaneous recoding of FITC-sinistrin after i.v. bolus injection at 22 weeks of age. Urine ACR measured in spot urine samples collected before termination 24 weeks of age. Terminal kidney samples were collected for 3D image analyses, histopathological evaluation, and next generation sequencing for gene expression analyses. Results GFR measurements indicated hyperfiltration in all AAV-injected UNx db/db mice compared to db/+ mice, while ReninAAV tended to dose-dependently decrease GFR compared to LacZAAV in UNx db/db mice. Urine ACR was worsened by ReninAAV-induced hypertension compared to LacZAAV controls. Automized AI-based glomerulosclerosis scoring showed ReninAAV dose-dependent increases in glomerulosclerosis compared to LacZAAV controls. 3D kidney imaging demonstrated increased glomerular volume in LacZAAV UNx db/db mice compared to db/+ mice with no further effect in ReninAAV groups. RNA sequencing revealed upregulated gene expression markers of fibrogenesis (incl. Col1a1, Col3, Col4, Fn1, Lamc2 and Vim) and tubular injury markers (Ngal and Kim-1), as well as downregulation of proximal tubular markers (Megalin and Aqp1) in ReninAAV UNx db/db mice compare to LacZAAV controls. Conclusion ReninAAV-induced hypertension in female UNx db/db mice accelerates kidney injury in uninephrectomized db/db mice and aggravates GFR, albuminuria and glomerulosclerosis in parallel with increased expression of genes associated with tubular injury renal fibrosis. Together, these data confirm that ReninAAV UNx db/db mice is a reliable model of DN with features of late stage human disease.

scholarly journals Punicalagin Ameliorates Lupus Nephritis via Inhibition of PAR2

2020 ◽  
Vol 21 (14) ◽  
pp. 4975
Author(s):  
Yohan Seo ◽  
Chin Hee Mun ◽  
So-Hyeon Park ◽  
Dongkyu Jeon ◽  
Su Jeong Kim ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Cell Line ◽  
Lupus Erythematosus ◽  
High Throughput Screening ◽  
Intraperitoneal Administration ◽  
Kidney Injury ◽  
High Rate ◽  
Beneficial Effects ◽  
Stage Renal Disease ◽  
End Stage

Lupus nephritis (LN) is the most frequent phenotype in patients with systemic lupus erythematosus (SLE) and has a high rate of progression to end-stage renal disease, in spite of intensive treatment and maintenance therapies. Recent evidence suggests that protease-activated receptor-2 (PAR2) is a therapeutic target for glomerulonephritis. In this study, we performed a cell-based high-throughput screening and identified a novel potent PAR2 antagonist, punicalagin (PCG, a major polyphenol enriched in pomegranate), and evaluated the effects of PCG on LN. The effect of PCG on PAR2 inhibition was observed in the human podocyte cell line and its effect on LN was evaluated in NZB/W F1 mice. In the human podocyte cell line, PCG potently inhibited PAR2 (IC50 = 1.5 ± 0.03 µM) and significantly reduced the PAR2-mediated activation of ERK1/2 and NF-κB signaling pathway. In addition, PCG significantly decreased PAR2-induced increases in ICAM-1 and VCAM-1 as well as in IL-8, IFN-γ, and TNF-α expression. Notably, the intraperitoneal administration of PCG significantly alleviated kidney injury and splenomegaly and reduced proteinuria and renal ICAM-1 and VCAM-1 expression in NZB/W F1 mice. Our results suggest that PCG has beneficial effects on LN via inhibition of PAR2, and PCG is a potential therapeutic agent for LN.

scholarly journals Inflammation and Oxidative Stress in Obesity-Related Glomerulopathy

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Jinhua Tang ◽  
Haidong Yan ◽  
Shougang Zhuang
Keyword(s):  
Oxidative Stress ◽  
Cell Function ◽  
Kidney Injury ◽  
Biologically Active ◽  
Renal Diseases ◽  
Low Grade ◽  
Chronic Oxidative Stress ◽  
Stage Renal Disease ◽  
End Stage ◽  
And Oxidative Stress

Obesity-related glomerulopathy is an increasing cause of end-stage renal disease. Obesity has been considered a state of chronic low-grade systemic inflammation and chronic oxidative stress. Augmented inflammation in adipose and kidney tissues promotes the progression of kidney damage in obesity. Adipose tissue, which is accumulated in obesity, is a key endocrine organ that produces multiple biologically active molecules, including leptin, adiponectin, resistin, that affect inflammation, and subsequent deregulation of cell function in renal glomeruli that leads to pathological changes. Oxidative stress is also associated with obesity-related renal diseases and may trigger the initiation or progression of renal damage in obesity. In this paper, we focus on inflammation and oxidative stress in the progression of obesity-related glomerulopathy and possible interventions to prevent kidney injury in obesity.

scholarly journals MO067DELETION AND BLOCKAGE OF KININ B1 RECEPTOR EXACERBATES CISPLATIN-INDUCED CKD

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Gabriel Estrela ◽  
Alexandre Budu ◽  
Leandro Freitas-Lima ◽  
Adriano Arruda ◽  
Mauro Perilhão ◽  
...  
Keyword(s):  
Renal Injury ◽  
Tubulointerstitial Fibrosis ◽  
Renal Diseases ◽  
Beneficial Effects ◽  
Protein Excretion ◽  
B1 Receptor ◽  
Inflammatory Stimuli ◽  
Kinin B1 Receptor ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background and Aims Kinins plays a major role in immune response, where kinin B2 receptor is constitutively expressed and kinin B1 receptor is induced under inflammatory stimuli. Kinin B1 receptor deletion and blockage has been shown to have beneficial effects in some models of renal diseases. Multiple acute renal insults, even if followed by renal recovery, is a risk factor for the future development of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Our main objective was to determine the importance of kinin B1 receptor in tubulointerstitial fibrosis induced by ongoing cisplatin treatment. Method Male C57/Bl6 mice were divided in 3 groups, vehicle, cisplatin, cisplatin + R715 (kinin B1 receptor antagonist). Animals has been treated with multiple doses of cisplatin (7mg/kg i.p) once a week during 4 weeks and R715 (0.8mg/kg i.p) 48, 24 and 1 hour prior to cisplatin injections. We also used B1KO mice (C57Bl6 background) and WT mice (littermates). Mice were euthanized after 30 days of last cisplatin injection. Renal parameters, histology, real time PCR were performed to investigate renal injury, inflammation and fibrosis. Results Cisplatin treatment increases most of renal parameters, renal injury and fibrosis markers. Deletion of B1 receptor exacerbates significantly creatinine (WT CIS 0,60+0,03 B1KO 0,76+0,01 mg/dL), urea (WT CIS 111,8+5,638 B1KO CIS 240,8+28,60 mg/dL), and protein excretion (WT CIS 0,0058+0,0011 B1KO CIS 0,0121+0,0007 mg/24h). Association of cisplatin with R715 increased creatinine levels (veh 0,43+0,03 cis+R715 0,64+0,04 mg/dL), exacerbates urea (cis 95,51 + 3,926 cis+R715 158,9+14,40 mg/dL) and protein excretion (cis 0,012+0,002 cis+R715 0,018+0,003 mg/24h). Renal injury markers such as KIM-1 and TNF-a showed no significant differences. NGAL expression exacerbates (cis 2,53+0,44 cis+R715 5,66+1,34) and tubular injury score (cis 0,130+0,021 cis+R715 0,191+0,020) is higher in cisplatin+R715 group. Fibrosis markers a-SMA (cis 2,56+0,43 cis+R715 4,67+0,99), Col4 (cis 2,57+0,39 cis+R715 5,14+1,01) and Vimentin (2,69+0,31 cis+R715 4,62+0,98) were exacerbated in cisplatin treatment associated with R715. Picrosirius red staining were used to asses tubulointerstitial fibrosis, and we confirmed that R715 treatment here also exacerbates fibrosis (cis 0,225+0,025 cis+R715 0,345+0,042). Conclusion Here we show that both deletion and blockage of kinin B1 receptor has deleterious effects in renal injury and fibrosis induced by ongoing cisplatin treatment.

scholarly journals EVALUATION OF CAPD AS RENAL REPLACEMENT THERAPY IN CHILDREN

2012 ◽  
Vol 19 (2) ◽  
Author(s):  
Risky Vitria Prasetyo ◽  
Noershanti Ramadhani ◽  
Ninik Asmaningsih Soemyarso ◽  
Mohammad Sjaifullah Noer
Keyword(s):  
Peritoneal Dialysis ◽  
Renal Disease ◽  
Cause Of Death ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Chronic Glomerulonephritis ◽  
Stage Renal Disease ◽  
End Stage ◽  
Lost To Follow Up

Objective: To evaluate the outcome of pediatric patients treated with continuous ambulatory peritoneal dialysis (CAPD) performed by experienced pediatric urologists. Material & Method: A retrospective study of children with end-stage renal disease (ESRD) by peritoneal dialysis (PD) in Division of Nephrology Department of Child Health, Faculty of Medicine Airlangga University, Soetomo Hospital, Surabaya, from January 2003 to February 2012 was conducted. Children with acute kidney injury treated by PD were excluded.Data reviewed were age, sex, primary renal disease, age at start of CAPD, duration of CAPD, outcome and cause of death. Descriptive statistics were used to analyze the data.Results: Twenty seven cases of children with CAPD within 9-year period were included. Most patients were 11-15 years old with 62,9% being male. Chronic glomerulonephritis and nephrotic syndrome were the main primary renal diseases. Fifteen (55,6%) patients had peritonitis. The longest duration on CAPD was 53 months. Outcome of 27 children was as follows, 11 patients died (40,8%), 8 patients survived (29,6%), and another 8 were lost to follow-up (29,6%). All (100%) patients had cardiovascular abnormalities as cause of death. Conclusion: The outcome and mortality rate of children with CAPD remain unfavourable. This is a challenge still to be overcomed. Keywords: Continuous ambulatory peritoneal dialysis, children, outcome.   

scholarly journals Quantification and Dosing of Renal Replacement Therapy in Acute Kidney Injury: A Reappraisal

2017 ◽  
Vol 44 (2) ◽  
pp. 140-155 ◽  
Author(s):  
William R. Clark ◽  
Martine Leblanc ◽  
Zaccaria Ricci ◽  
Claudio Ronco
Keyword(s):  
Acute Kidney Injury ◽  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Journal Club ◽  
Kidney Injury ◽  
Accurate Estimation ◽  
Stage Renal Disease ◽  
End Stage ◽  
Dose Assessments ◽  
Solute Clearance

Background/Aims: Delivered dialysis therapy is routinely measured in the management of patients with end-stage renal disease; yet, the quantification of renal replacement prescription and delivery in acute kidney injury (AKI) is less established. While continuous renal replacement therapy (CRRT) is widely understood to have greater solute clearance capabilities relative to intermittent therapies, neither urea nor any other solute is specifically employed for CRRT dose assessments in clinical practice at present. Instead, the normalized effluent rate is the gold standard for CRRT dosing, although this parameter does not provide an accurate estimation of actual solute clearance for different modalities. Methods: Because this situation has created confusion among clinicians, we reappraise dose prescription and delivery for CRRT. Results: A critical review of RRT quantification in AKI is provided. Conclusion: We propose an adaptation of a maintenance dialysis parameter (standard Kt/V) as a benchmark to supplement effluent-based dosing of CRRT. Video Journal Club “Cappuccino with Claudio Ronco” at http://www.karger.com/?doi=475457

scholarly journals Identification of Novel Biomarker for Early Detection of Diabetic Nephropathy

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 457
Author(s):  
Kyeong-Seok Kim ◽  
Jin-Sol Lee ◽  
Jae-Hyeon Park ◽  
Eun-Young Lee ◽  
Jong-Seok Moon ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Early Stage ◽  
Kidney Injury ◽  
Diabetic Patients ◽  
High Morbidity ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Zucker Diabetic Fatty Rats ◽  
Kidney Injury Molecule 1 ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. After development of DN, patients will progress to end-stage renal disease, which is associated with high morbidity and mortality. Here, we developed early-stage diagnostic biomarkers to detect DN as a strategy for DN intervention. For the DN model, Zucker diabetic fatty rats were used for DN phenotyping. The results revealed that DN rats showed significantly increased blood glucose, blood urea nitrogen (BUN), and serum creatinine levels, accompanied by severe kidney injury, fibrosis and microstructural changes. In addition, DN rats showed significantly increased urinary excretion of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Transcriptome analysis revealed that new DN biomarkers, such as complementary component 4b (C4b), complementary factor D (CFD), C-X-C motif chemokine receptor 6 (CXCR6), and leukemia inhibitory factor (LIF) were identified. Furthermore, they were found in the urine of patients with DN. Since these biomarkers were detected in the urine and kidney of DN rats and urine of diabetic patients, the selected markers could be used as early diagnosis biomarkers for chronic diabetic nephropathy.

scholarly journals Renoprotective Effects of DPP-4 Inhibitors

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 246
Author(s):  
Daiji Kawanami ◽  
Yuichi Takashi ◽  
Hiroyuki Takahashi ◽  
Ryoko Motonaga ◽  
Makito Tanabe
Keyword(s):  
Diabetic Kidney Disease ◽  
Experimental Studies ◽  
Review Article ◽  
Glucose Lowering ◽  
Beneficial Effects ◽  
Glucose Levels ◽  
Membrane Bound ◽  
Stage Renal Disease ◽  
End Stage

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) worldwide. Dipeptidyl peptidase (DPP)-4 inhibitors are widely used in the treatment of patients with type 2 diabetes (T2D). DPP-4 inhibitors reduce glucose levels by inhibiting degradation of incretins. DPP-4 is a ubiquitous protein with exopeptidase activity that exists in cell membrane-bound and soluble forms. It has been shown that an increased renal DPP-4 activity is associated with the development of DKD. A series of clinical and experimental studies showed that DPP-4 inhibitors have beneficial effects on DKD, independent of their glucose-lowering abilities, which are mediated by anti-fibrotic, anti-inflammatory, and anti-oxidative stress properties. In this review article, we highlight the current understanding of the clinical efficacy and the mechanisms underlying renoprotection by DPP-4 inhibitors under diabetic conditions.

Peritoneal Dialysis

2019 ◽  
Author(s):  
Karlien François ◽  
Joanne M. Bargman
Keyword(s):  
Renal Failure ◽  
Peritoneal Dialysis ◽  
Peritoneal Cavity ◽  
Fluid Overload ◽  
Kidney Injury ◽  
Dialysis Fluid ◽  
Keywords Peritoneal Dialysis ◽  
Stage Renal Disease ◽  
End Stage ◽  
Developed World

In peritoneal dialysis (PD), the peritoneum serves as a biological dialyzing membrane. The endothelium of the vast capillary network perfusing the peritoneum functions as a semipermeable membrane and allows bidirectional solute and water transfer between the intravascular space and dialysate fluid dwelling in the peritoneal cavity. PD is a renal replacement strategy for patients presenting with end-stage renal disease. It can also be offered for ultrafiltration in patients with diuretic-resistant fluid overload even in those without advanced renal failure. PD can also be used for patients with acute kidney injury, although in the developed world this occurs rarely compared to the use of extracorporeal therapies. This review contains 9 videos,  8 figures, 4 tables, and 73 references.  Keywords: peritoneal dialysis, peritoneal cavity, catheter, dialysis fluid, ultrafiltration, tunnel infection, osmotic pressure, renal failure

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