Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 3rd International Conference on Nephrology & Therapeutics Valencia, Spain.

Day 1 :

  • Track 1: Hypertension, CKD and Diabetes
    Track 2: Fluids & Electrolytes
Location: Valencia, Spain
Speaker

Chair

Anil K Mandal

Mandal Diabetes Research Foundation, USA

Speaker

Co-Chair

Xavier Debussche

CHU St Denis, Reunion Island

Speaker
Biography:

Xavier Debussche is specialist in Endocrinology and Metabolism, head of Department, Chronic Pathologies and Metabolic Diseases, and clinical research manager in the University hospital of the Reunion Island. He took part as principal or associate Investigator in several epidemiological research, randomized controlled trials, and mixed method studies. He has published more than 30 scientific articles referenced in Medline. He has participated actively in the development and structuring of care networks with a global integrative approach in chronic diseases.

Abstract:

Chronic kidney disease is a major public health problem. This observational epidemiological study aimed to evaluate the prevalence of proteinuric nephropathy in patients with type 2 diabetes by consulting community-based general practitioners in French overseas departments and territories (DOM-TOM). Screening was carried out with reagent strips Albustix® for proteinuria and, in case of trace amounts or a negative result, Microalbustix® for microalbuminuria. Ninety one general practitioners participated in the study and 402 patients were included (54% female, mean age 60.1±11.2 years). Duration of diabetes was 8.9±6.6 years and mean HbA1c was 7.3±1.4% (52.2% with HbA1c < 7%). Screening was positive for 45.7% of the patients: 23.6% positive for proteinuria with Albustix® [95%CI: 19.5%; 27.8%] and 22.1% with Microalbustix® [95%CI: 18.1%; 26.2%] (macroalbuminuria 6.2% [95%CI: 4.1%; 9.0%], microalbuminuria 15.9% [95%CI: 12.5%; 19.9%]. In conclusion, screening with reagent strips revealed that nearly half of the patients had proteinuria or albuminuria, thus confirming the high prevalence of nephropathy in type 2 diabetes patients living in the DOM-TOM and illustrating the need for frequent renal function screening in type 2 diabetics in general medicine for the prevention of chronic kidney disease.

Pupalan Iyngkaran

Flinders University School of Medicine, Australia

Title: Region specific cardiology perspectives on the cardiorenal syndrome - Challenges and solutions

Time : 11:20-11:40

Speaker
Biography:

Pupalan Iyngkaran is a Consultant Cardiologist and Senior Lecturer with subspecialty training in Heart Failure (CHF) and Cardiovascular Imaging with the Royal Darwin Hospital and Flinders University. He trained in cardiology at the Queen Elizabeth Hospital, South Australia and National Heart Centre, Singapore; with additional subspecialty training in echocardiography and HF research at the Flinders Medical Centre and Monash University. His research has involved basic science work on uremic toxins on cardiac myocytes, novel renal injury biomarkers, prospective databases, Indigenous patient journey mapping and translating regional specific disease management programs including self-care programs for CHF.

Abstract:

Congestive Heart Failure (CHF), a leading cause of morbidity and mortality in the Northern Territory (NT) and developed world, when confounded with concomitant renal insufficiency is associated with significant additional risk. The NT and remote Australia has a unique multiethnic demography, including a sizeable Indigenous population, spread over large geographical distances. Sixty percent live in 2 major towns serviced by 2 major public hospitals. Additional factors that can affect CHF management are prevalent in remote areas and are not well addressed within randomized controlled trials. The prevalence of renal insufficiency in CHF in the NT is significant. Accurate prospective data is lacking, however is likely greater than 40%. Co-morbid contributors and associations, in particular DM, HT, IHD, RHD, contribute further to the increased risks. Challenges continue to exist in accurately estimating the size of the problems, accurate diagnostics, disease prevention, and chronic disease management. This talk is focused on: firstly, exploring the size of the problem; secondly, exploring the available evidence from the major randomized CHF pharmaceutical trials; thirdly, a brief review of diagnostic renal injury and functional markers; and finally, exploring simple therapeutic options. The focus of these discussions has regional specific themes, however the broader themes may have universal appeal. A need to consider a wider therapeutic paradigm, from the standard guidelines is also discussed, as novel therapeutic options have been relatively slow to come by.

Speaker
Biography:

Elisa Mieko Suemitsu Higa graduated from Medical School in São Paulo, Brazil. After obtaining the Master and PhD degree at the Nephrology Division of Universidade Federal de São Paulo (UNIFESP), she has been at University of Colorado Health Sciences Center in Denver, Colorado, USA, for a Post Doctoral Program. Currently, she works at UNIFESP as an Associate Professor of Medicine Department, where she is the Supervisor for the 6th year students from Medical School, at the Emergency Division (Internship). She is the Chief of Nitric Oxide and Oxidative Stress Laboratory and is involved in the Translational Medicine and Nephrology Post graduation Programs. She is an elected member of Physiology/ Physiopathology Department of Brazilian Society of Nephrology. She served as a peer reviewer for Scientific Journals like PLOS ONE, Nitric oxide, ETAP and Medical Principles and Practice.

Abstract:

Previous studies in our laboratory showed that N-acetylcysteine supplementation or aerobic training reduced oxidative stress and the progression of diabetic nephropathy in rats. The P2X7 receptor is up-regulated in pathological conditions, such as diabetes mellitus. This up-regulation is related to oxidative stress and induces tissue apoptosis or necrosis. The aim of the present study is to assess the role of P2X7 receptor in the kidneys of diabetic rats submitted to aerobic training and/or N-acetylcysteine (NAC) supplementation. Diabetes was induced in male Wistar rats by streptozotocin (60mg/kg, i.v.) and the training was done on a treadmill; NAC was given in the drinking water (600mg/L). By confocal microscopy, as compared to control, the kidneys of diabetic rats showed increased P2X7 receptor expression and a higher activation in response to 2’(3’)-O-(4-benzoylbenzoyl) adenosine5’-triphosphate (specific agonist) and adenosine triphosphate (nonspecific agonist) (all p<0.05). All these alterations were reduced in diabetic rats treated with NAC, exercise or both. Proteinuria, albuminuria (early marker of diabetic nephropathy) and creatinine clearance in DM groups were attenuated with these treatments. Lipoperoxidation was strongly correlated with P2X7 receptor expression, which was also correlated to NO•, thus associating this receptor to oxidative stress and kidney lesion. We suggest that P2X7 receptor inhibition associated with the maintenance of redox homeostasis could be useful as coadjuvant treatment to delay the progression of diabetic nephropathy.

You-Hua Xu

Macau University of Science and Technology, China

Title: Study of phytoestrogens on ameliorating advanced glycation end products-induced HUVECs damage

Time : 12:00-12:20

Speaker
Biography:

You-Hua Xu has completed his PhD at the age of 29 years from Macau University of Science and Technology and now serving as Assistant Professor and PI at State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology. He has published more than 30 papers in reputed journals. He is an expert reviewer for several scientific journals.

Abstract:

Vasculopathy, including endothelial cell apoptosis and inflammation contributes to the high incidence of stroke and myocardial infarction in diabetic patients. Abundant studies have demonstrated the pivotal role of advanced glycation end products (AGEs) on the development of diabetic-vasculopathy. The author and team demonstrated in their study that calycosin, a phytoestrogen, can ameliorate AGEs-induced HUVECs damage. By fluorescence polarization and fluorescence absorption assays, it was observed that calycosin interacted with AGEs in a time-dependent manner. Further studies found that calycosin entered into the cells as detected by HPLC. By MTT method, it was found that calycosin significantly ameliorated AGEs-induced HUVECs apoptosis. Calycosin preincubation dramatically increased anti-apoptotic Bcl-2 while decreased pro-apoptotic Bax & Bad expressions as detected by immunocytochemistry. Moreover, calycosin ameliorated macrophage migration and adhesion to HUVECs; the monocyte chemotactic protein-1 and interleukin-6 levels in the culture supernatant were dramatically reduced by calycosin as determined by ELISA; and the expressions of inflammatory proteins including ICAM-1, TGF-β1 and RAGE at both protein and mRNA levels were significantly reduced to the normal level by calycosin pretreatment as determined by immunocytochemistry and real-time RT-PCR. The intracellular investigation suggested that calycosin could reverse AGEs-activated ERK1/2 and NF-κB p65 phosphorylation and nucleus translocation, in which estrogen receptors were involved in. The present study strongly indicates that calycosin can enter into the cell and modulate endothelial cell dysfunction by ameliorating AGEs-induced cell apoptosis and inflammation.

Speaker
Biography:

Michael F Michelis is Director of Nephrology at Lenox Hill Hospital in New York and Clinical Professor of Medicine at New York University School of Medicine. He received his training in renal disease at the University of Pittsburgh and was a member of the faculty there before moving to New York. He is a Fellow of the American College of Physicians, a Specialist in Clinical Hypertension and a Fellow of the American Society of Nephrology. He has been principal investigator on many clinical trials and has authored numerous publications. He directed clinical studies which characterized an unrecognized genetic kidney disease now referred to as Michelis-Castrillo Syndrome.

Abstract:

Hypernatremia is a common electrolyte disorder associated with adverse outcomes. Our aim was to investigate known prognostic factors as well as other variables which we identified in hospitalized hypernatremic geriatric patients and their relationship to patient outcomes. A retrospective chart review of all adult hospitalized patients in a 4 month period with a serum sodium level >150 mmol/L was performed. Factors evaluated included use of a nephrology consultation, urine laboratory measures, fluids employed, rate of correction, and patient’s care setting. The patient mortality rate was 52%. Mean age was 79.6 years (n=33) and mean initial sodium level was 152.6 mmol/L. Five of 15 patients who received nephrology consultation survived, while 11 of 18 patients without a nephrology consultation survived (p=0.12). Plasma and urine osmolality, and urine sodium concentration were checked in less than 25% of patients. Of the 23 patients (70%) who had their serum sodium level corrected, 11 were corrected in ≤3 days and 12 in >3 days but this difference did not affect mortality rate (45% vs 50%, p=0.99). Fifteen of 18 patients in the ICU expired whereas only 2 of 15 patients not in the ICU expired (p < 0.001). Hypernatremia is associated with a poor prognosis and outcomes are still disappointing despite appropriate rates of correction, intensive care monitoring, and the involvement of a nephrologist. Preventive measures directed at avoidance of the development of hypernatremia may provide significant patient benefit.

Break:
Lunch Break 12:40-13:20

Anil K Mandal

Mandal Diabetes Research Foundation, USA

Title: Effect of sodium bicarbonate infusion in reversal of acute renal failure

Time : 13:20-13:40

Speaker
Biography:

Anil K Mandal is a native of India and a naturalized citizen of the United States. He is board certified in Internal Medicine and Nephrology (kidney disease and hypertension). He is an author of a dozen books and more than 100 published articles on research in diabetes and kidney disease. He is a two-time Fulbright Scholar and a visiting professor in 23 countries that invited him to lecture on diabetes, high blood pressure, and kidney diseases.

Abstract:

End stage renal disease (ESRD) is increased in diabetes despite use of renin-angiotensin axis (RAAS) inhibitor drugs which are considered to be renoprotective drugs. Acute renal failure (ARF) has been reported as a risk factor contributing to ESRD in diabetes. The purpose of this presentation is to demonstrate that ARF is reversible with slight or no risk for progression to ESRD. The aim here is to show that sodium bicarbonate infusion is an effective therapy in reversal of ARF. Three patients with ARF, two associated with RAAS inhibitor therapy and one associated with radio contrast material are described. In the RAAS inhibitor treated patients eGFR varied from 10-12 ml/min upon hospital admission, both had metabolic acidosis. In the one with radiocontrast study eGFR decreased from baseline 31 ml per min to 16 ml/min 48 hours after the use of contrast. All of them were treated with Sodium Bicarbonate Infusion (900 ml isotonic saline and 100 l [100 MEQ] Sodium bicarbonate in a liter bag) at a rate of 75 ml for 72 hours, then at 50 ml/hour for another 48 hours. Serial renal function parameters and electrolytes were obtained. Renal function improved to baseline or better in all three patients. eGFR increased to 53, 56 and 48 ml/min (n≥60ml/ min), respectively. In one of the two RAAS treated patients, ARF redeveloped in 48hours after she retook RAAS inhibitor drug by mistake after returning home. eGFR decreased from 56 ml/min to 14 ml/min improving again to 34 ml/min with sodium bicarbonate infusion for 48 hours. In conclusion, sodium bicarbonate infusion is efficacious in reversing ARF of diverse etiology. Recovery is rapid when ARF is associated with metabolic acidosis, suggesting buffering of hydrogen ions is a facilitator of renal function recovery.

Speaker
Biography:

Giovanni Sansoè graduated in Medicine (University of Torino, Italy) in 1990 and specialized in Gastroenterology and Digestive Endoscopy (University of Modena, Italy) in 1996. He completed a Fellowship in Hepatology (University of Toronto, Canada) in 2005. He worked as Clinical Associate Professor for a few months (University of Calgary, Canada) in 2008. He is a Clinical Hepatologist of the Gradenigo Hospital, University of Torino, Italy. He has published more than 30 papers in reputed journals dealing with the renal complications of portal hypertension. He serves as invited reviewer for the following medical journals: Gut, J Hepatol, Am J Kidney Dis, and others.

Abstract:

Background: Catecolamines and angiotensin II overproduction reduces fluid delivery to the Henle’s loop and renal excretion of solute-free water. In ascitic cirrhosis, hypersecretion of vasopressin (ADH) is thought to rule tubular free-water reabsorption (TFWR), but ADH V2-receptor antagonists are not beneficial in the long-term treatment of hyponatremic ascites. Aim: We explore the hypothesis that excess TFWR in ascitic cirrhosis could depend on proximal tubular fluid retention rather than on ADH hypersecretion. Methods: 60 ascitic cirrhotic rats were carefully assessed: rats receiving 13-week CCl4 administration only (group G1), cirrhotic rats receiving daily diuretics (0.5 mg/kg furosemide + 2 mg/kg K+-canrenoate during the 11th-13th weeks of CCl4) (G2), cirrhotic rats treated with diuretics + daily oral guanfacine, α2-adrenergic receptor agonist and sympatholytic agent, 2 (G3), 7 (G4), or 10 mg/kg (G5); ascitic rats treated with diuretics + SSP-004240F1, vasopressin V2-receptor antagonist, 1 mg/kg (G6). Results: Diuretics + V2 antagonists (in G6) and diuretics + guanfacine 2 mg/kg (in G3) reduced TFWR from 32±11 (in G1) to 21±9 and to 20±8 microL/min, respectively (P<0.03). Compared to G2, the addition of guanfacine (2 mg/kg) (in G3) to diuretics reduced serum norepinephrine from 423±122 to 211±111 ng/L (P<0.01), plasma renin activity from 25±12 to 9±7 ng/mL/h (P<0.03), and TFWR from 45±18 to 20±8 microL/min (P<0.01). In the population of 60 rats, TFWR did not correlate with ADH levels (r=0.12, P: n.s.), but showed correlations with plasma aldosterone (r=0.51, P<0.01), urinary potassium excretion rate (r=0.90, P<0.001), and osmolar clearance (r=0.93, P<0.001). Conclusions: Increased distal delivery of fluid, achieved through a reduction in adrenergic function and renin levels, is as effective as ADH V2-receptor blockade to blunt excess TFWR in ascitic cirrhosis.

Pauline Abou- Jaoude

University Medical Center-Rizk Hospital, Lebanon

Title: Solitary kidney: The human model of hyperfiltration injury

Time : 14:00-14:20

Speaker
Biography:

Pauline Abou-Jaoudé graduated in 2003 and received her MD in Pediatrics in 2007 from the Saint-Joseph University Medical School, Beirut, Lebanon. Between November 2006 and October 2008, she completed her fellowship in Pediatric Nephrology at “Centre de Référence des Maladies Rénales Rares”, Hospices Civils de Lyon, under the patronage of Pr. Pierre Cochat. In 2010, she worked as an attending physician in the Pediatric Nephrology Division of the “Femme - Mère - Enfant” University hospital in Bron, France. Since 2012, she works as a Senior Consultant in Pediatric Nephrology at the University Medical Center - Rizk Hospital, and in several other hospitals in Beirut, Lebanon. She is also an Assistant Professor of Pediatrics at the Lebanese American University. She has several publications in international peer reviewed journals and textbooks. She is a member of the French (SNP), the European (ESPN) and the International (IPNA) Societies of Pediatric Nephrology.

Abstract:

Background: Serious concerns have risen during the last decades regarding the potential role of solitary kidney (SK) in promoting systemic hypertension, proteinuria and glomerulosclerosis, as late consequences of the subsequent hyperfiltration injury. However, published reports focusing on this issue remain scarce, especially in children, and results are somewhat controversial. To address this matter, we conducted a retrospective chart review of children with radiologically normal SK in order to assess their mid- and long-term outcome. Methods: From 127 children with a single functioning kidney referred for renal work-up during a study period of 17 years, only 97 (43 females) with a mean age of 10.3±4.3 years (median: 10 years, range: 2.9-25.5) were enrolled in the study. The others were excluded because of evidence of structural and/or parenchymal abnormalities in the remnant kidney. Forty four children of 97 had a congenital SK with no prior history of urinary tract infection (21 unilateral renal agenesis and 23 multicystic dysplastic kidney) and 53 had undergone unilateral nephrectomy for renal tumor (n=41) or complicated urological structural abnormality (n=12). All children had undergone a full renal assessment including Blood Pressure (BP), glomerular filtration rate (GFR) determined by inulin clearance, and microalbuminuria measured as albumin-to-creatinine ratio (alb/crea). The data were collected from medical records at last functional assessment. Results: After a mean follow-up time with SK (years-at-risk) of 8.7±3.9 years (median: 8.1 years, range: 1.5-21.2), only 2 children (2%) were found to have systemic hypertension confirmed by 24-h ambulatory BP monitoring. The mean alb/crea ratio was 2.3±4.6 mg/mmol (median: 1.2 mg/mmol, range: 0.1-27.7). Seventeen patients (17.5%) had a significant microalbuminuria above the threshold of 2 mg/mmol urine creatinine. Seven children (7.2 %) had a GFR <80 mL/min/1.73 m2, all had been nephrectomized in early childhood. The overall mean GFR was 100.6±15 mL/min/1.73 m2 and was found to be inversely correlated with age and follow-up time (years-at-risk), suggesting a gradual decline in renal function over time. This inverse relationship kept true even after excluding children having received nephrotoxic antimitotic agents with or without radiation therapy. Conclusions: In the light of these results, it appears that renal function in children with normal SK is well preserved on the short- and medium-term, but it seems to decline gradually with longer periods of follow-up. Thus, careful monitoring should be proposed throughout childhood to detect early signs of glomerular hyperfiltration and prevent its progression to more serious complications.

Lena Jafri

Aga Khan University Hospital, Pakistan

Title: Diagnostic potential of natriuretic peptides in patients with impaired kidney function

Time : 14:20-14:40

Speaker
Biography:

Lena Jafri has proven her worth at the Department of Pathology and Microbiology, Aga Khan University Hospital as a young energetic resource. She graduated from Dow Medical College and ascended the ladder of success taking her first step in 2007 as a resident in Chemical Pathology AKUH, arose from the ranks as a Chief Resident, received ‘Best Resident Award’ and today she has transitioned to a faculty member. Her publications on chronic kidney disease and metabolic bone diseases have been effectively reviewed by her peers and are extremely vital for the developing countries like Pakistan.

Abstract:

Plasma B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are heart failure (HF) markers and also rise in chronic kidney disease (CKD), but the effect of these biomarkers is not fully understood in CKD patients. The aim of this study was to determine BNP and NT-proBNP cutoffs predictable of HF in CKD cohort and compare its concentration in different stages of CKD. Adults with estimated glomerular filtration rate <60 ml/min for ≥3 months were identified in consulting clinics from June 2009 to March 2010. HF was defined as documented by a cardiologist with ejection fraction <40% and assessed by New York Heart Association classification (NYHA). A total of 190 subjects were enrolled in the study, 95 with and 95 without HF. The mean age of patients was 58 (±15) years, 67.4% being males. Mean BNP levels showed a 2.5 fold and 1.5 fold rise from CKD stage 3 to stage 5 in patients with and without HF respectively. NT-proBNP levels in non-HF group were 3 fold higher in CKD stage 5 compared to stage 3. Mean NT-proBNP levels were 4 fold higher in CKD stage 5 compared to stage 3 in patients with HF. Optimal BNP and NT-proBNP cutoffs for HF diagnosis for the entire CKD group were 300 pg/ mL and 4502 pg/mL respectively. BNP and NT-proBNP were elevated in patients with impaired kidney function even in the absence of HF and further increased stepwise with NYHA severity. However the magnitude of increase in NT-proBNP was greater than that of BNP.

Navneet Sharma

Delhi Institute of Pharmaceutical Sciences and Research, India

Title: Transdermal patches based on solid lipid nanoparticles of Metformin: Novel approach for drug delivery of Type 2 diabetes

Time : 14:40-15:00

Speaker
Biography:

Navneet Sharma has completed his B. Pharma at the age of 22 years from Gautama Buddha Technical University, Lucknow, UP and his M. Pharma from JSS College of Pharmacy, JSS University, Mysore, Karnatka and Post graduate diploma in Drug regulatory affairs from Jamia Hamdard New Delhi. He has published and presented several papers in reputed journals and conferences. Currently he is doing his research as a research fellow from Institute of Nuclear Medicine and Allied Science DRDO, New Delhi, india.

Abstract:

Worldwide prevalence of type 2 diabetes is increasing with alarming proportions. Metformin is the first-line oral antidiabetic drug of choice for the treatment of type 2 diabetes.The objectives of the present study were to develop Metformin solid lipid nanoparticles (M-SLN) and incorporate it in the transdermal patches. M-SLN was evaluated for Particle size, Zeta potential, Surface morphology by scanning electron microscopy (SEM), Transmission electron microscopy (TEM) and In vitro- In vivo release studies. Patches were evaluated by Ex-vivo skin permeation studies. M-SLN was prepared by solvent diffusion technique using propylene glycol (solvent), polymethacrylic acid (polymer) and Soya lecithin (lipid base). After doing the evaluation of the above mentioned pharmaceutical parameters, M-SLN was loaded in Methocel K100M transdermal patches. Ex-vivo skin permeation studies were conducted on male Wistar rat’s skin using Franz-type diffusion Cells. The particle size of M-SLN varied among the formulation due to variation in the composition of formulations. Zeta potential of best formulation was found to be +27mV. SEM and TEM indicates discrete spherical structure without aggregation. Drug content was found to be 1.45mg/patch. The ex-vivo permeation studies indicate that the high cumulative amount of drug is permeated from M-SLNs. Our study proves the successful delivery of M-SLN from transdermal patch, and Histopathological studies confirmed that the M-SLN transdermal patch only provoked an acceptable modest inflammatory response. These results support the feasibility of developing transdermal metformin for human applications. Thus, transdermal delivery of M-SLN is a safe, painless and cost effective drug delivery system for diabetes patients.

Biography:

Joseph Justin H Regalado has completed his MD at the age of 23 years from the University of the Philippines, Philippine General Hospital. He is currently in his 2nd year of residency training in Internal Medicine at the Cardinal Santos Medical Centre, Philippines.

Abstract:

Research question: In adult patients undergoing contrast procedures, will furosemide-based prophylaxis, compared with saline, reduce the risk of Contrast-Induced Nephropathy (CIN)? Background: CIN is the third leading cause of hospital-acquired kidney injury. While hydration is the most accepted prevention, several studies investigated using pharmacological adjuncts. An earlier meta-analysis done for Furosemide did not show significant benefit, but newer studies showed otherwise. Objectives: This meta-analysis assesses the potential of Furosemide in preventing CIN. Inclusion criteria: Studies published in English with available full texts were included, irrespective of blinding, based on: Populations older than 18 years, undergoing contrast procedures, and studies that defined CIN as creatinine increase more than 25%, or more than 0.5mg/dL. Search strategy: Pubmed, Cochrane, and Clinical Key were used to identify all randomized controlled trials (RCT), with human subjects, using furosemide in a contrast procedure. Search terms were “Furosemide”, “Contrast-Induced Nephropathy” and “Acute Kidney Injury”. Study manoeuvres: Author, procedure, design, furosemide regimen, and CIN incidence were extracted. Subcategories were created for further analysis. A minimum Jadad score of 3 was needed for acceptance. Statistical analysis: The incidence of CIN was treated as dichotomous variables, expressed as relative risks, with a 95% confidence interval (CI). Calculations were done using the Mantel-Haenszel random-effects model, using Cochrane’s RevMan 5.2. Results: 6 out of 16 papers were included based on the criteria mentioned (pooled n=1432). Meta-analysis of these trials showed that while the data trended towards a saline regimen, there is no significant difference (95% CI) in incidence reduction, with considerable heterogeneity (81%). Subcategory analysis was done to reduce heterogeneity. While each subplot did not show statistical significance, these showed patterns that suggest future strategies to explore. Conclusions: A regimen with the best chance of reducing CIN incidence used normal saline, per-kilogram weight hydration, and matched hydration. Pursuing RCT’s similar to the MYTHOS trial, PRINCE trial, and Guo’s study is recommended. With more studies with similar protocols, more conclusive results can be achieved.The limitations of this study include methodology heterogeneity, lack of peer article review, and available research.

Usman Bhutta

University of Oklahoma Health Sciences Center, USA

Title: Severe hypocalcemia due to Denosumab use in a patient with metastatic prostate cancer

Time : 15:20-15:40

Biography:

Abstract:

Denosumab is a monoclonal antibody used for prevention of skeletal-related events (SRE’s) in patients with bone metastases from solid tumors. Hypocalcemia is a rare and dangerous side effect of the drug denosumab. Here, a case of a patient with metastatic prostate cancer who developed severe hypocalcemia after the administration of the drug is presented. The patient’s vitamin D levels were low when checked after administration of the drug, which likely predisposed him to the development of hypocalcemia. He was placed on high doses of oral and intravenous (IV) calcium and vitamin D without any appreciable response in the serum calcium level. His ionized calcium remained below 0.71 mmol/L despite supplementation with oral and IV calcium. During the hospital course, he developed hydronephrosis from the spread of his tumor, did not want to undergo percutaneous nephrostomy tube placement; therefore, it was decided to dialyze him for acute renal failure and to correct his hypocalcemia. Checking calcium and vitamin D levels prior to the administration of denosumab is vital in preventing hypocalcemia. If hypocalcemia is severe and not responsive to high doses of vitamin D, oral and IV calcium, then hemodialysis with a high calcium bath can correct this electrolyte abnormality.

Break:
Coffee Break 15:40-15:55
  • Track 3: Genetics in Kidney Diseases
    Track 4: Chronic & Acute Renal Diseases
Location: Valencia, Spain
Speaker

Chair

Jean Claude Dussaule

INSERM, France

Speaker

Co-Chair

Ivan Sebesta

Charles University in Prague, Czech Republic

Session Introduction

Ivan Sebesta

Charles University in Prague, Czech Republic

Title: Diagnostic approach to Hereditary renal hypouricemia

Time : 15:55-16:15

Speaker
Biography:

Ivan Sebesta, MD has completed his PhD from First Medical Faculty, Charles University. He worked in Purine Research Laboratory, University of London. He has published more than 25 papers in reputed journals. He received Award of the Ministry of Health of Czech Republic for Science and Research in 1999. During the period 2004-07, he was the President of Purine & Pyrimidine Society. In 2005, he organized 10th Symposium of this Society in Prague. He works as deputy of head for teaching and is involved in research and clinical care of patients with inborn errors of metabolism.

Abstract:

Hereditary renal hypouricemia is a new genetic disorder affecting renal transport of uric acid (UA). This disorder predispose the patients to exercise-induced acute renal failure and/or nephrolithiasis. The known causes are defects in the SLC22A12 gene, encoding the human urate transporter 1 (hURAT1), and impairment of SLC2A9 gene, which encodes GLUT9 transporter. Diagnosis is based on hypouricemia (<119 μmol/l) and increased fractional excretion of UA (>10%). To date, this disorder have been reported in East Asia mainly. More than one hundred Japanese patients have been described. Hypouricemia is sometimes overlooked, therefore we have set up the flowchart. The patients were selected for molecular analysis from 660 hypouricemic patients. Other secondary causes of hypouricemia such as Fanconi syndrome or drug-induced tubulopathy were excluded. The estimations of : 1) serum UA, 2) excretion fraction of UA, 3) and analysis of SLC22A12 and SLC2A9 genes followed. We have found 3 transition, 4 deletions in SLC22A12 gene and two insertions in SLC2A9 gene in 9 Czech patients, which is the second group worldwide, in terms of number of patients. Three patients had acute renal failure and urate nephrolithiasis. In addition, we have detected two transitions in the SLC2A9 gene in two boys from UK. Conclusions: Hereditary renal hypouricemia is still unrecognized disorder and probably not wide spread in East Asia only. Asymptomatic hypouricemia may be a risk factor for kidney injury. Patients with unexplained hypouricemia need detailed purine metabolic investigations.

Speaker
Biography:

Satu Kuure completed her PhD in 2007 from Biomedical Institute at the University of Helsinki and continued her studies exploring the regulation of renal differentiation during the two-year Postdoc at Columbia University Medical Center where she focused on different imaging techniques and cellular events guiding renal branching morphogenesis downstream of receptor tyrosine kinase signaling. Currently, she is a team leader at the Institute of Biotechnology, University of Helsinki, and has published several critically important papers in top-end journal and serves as a board member of Finnish Society of Developmental Biology.

Abstract:

Reduced nephron account is a risk factor for renal defects, hypertension and diabetic nephropathies in later life. The final nephron count is determined by ureteric bud (UB) branching during fetal life, the process that specifies also the actual size and shape of the kidneys. Such dual role of UB branching is due to the nature of renal differentiation regulation, which is guided through classic reciprocal inductive tissue interactions. Nephrons differentiate from an established nephron progenitor cell (NPC) pool, which surround each tip of UBs, and their renewal capacity greatly affects the extent of UB branching. The research focuses on understanding cellular events that promote kidney differentiation at the level of UB branching and NPC self-renewal/differentiation in order to fully cover their interplay. The author will discuss about the molecular regulation of renal differentiation on the basis of our fresh advances in receptor tyrosine kinase (RTK) signaling and intracellular pathways activated downstream of RTKs. Highlights of the recent advances in glial cell-line derived neurotrophic factor (GDNF) activated RET signaling and mitogen-activated protein kinase (MAPK) functions within UB epithelium will be presented to support the hypothesis that MAPK pathway activated in scattered UB cells is involved in epithelial progenitor cell (EPC) regulation, and mediates at least some if not all of the GDNF-RET induced cellular functions during branching. Preliminary results of MAPK activity functions regulating NPC biology and finally conclusive suggestions for clinical importance/implementations of our research for renal hypofunction patients are presented.

Speaker
Biography:

Jeffrey G Dickhout received his PhD from McMaster University. He was the inaugural holder of the Division of Nephrology Junior Researcher award. He is currently an Assistant Professor in the Department of Medicine, Division of Nephrology at McMaster University and St. Joseph’s Healthcare Hamilton. His research program is currently supported by the Canadian Institutes of Health Research. He also holds the McMaster University, Department of Medicine Internal Career Research Award. He has published over 25 peer-reviewed papers.

Abstract:

ER stress has been shown to be associated with acute kidney injury (AKI) from a variety of causes including radio contrast, cisplatin, antibiotics and ischemia. We investigated if therapy with a known ER stress inhibitor, 4-Phenylbutyrate, would prevent AKI induced by the nucleoside antibiotic tunicamycin. Tunicamycin injection (I.P., 0.5 mg/kg) in the C57BL/6 mouse lead to AKI characterized histologically as acute tubular necrosis (ATN) occurring in the proximal convoluted tubule of the cortex as well as in the straight proximal tubule (Pars Recta) of the outer medullary stripe. This damage included tubular epithelial cell vacuolization, appearance of apoptotic nuclear as demonstrated by TUNEL staining, ER stress marker expression including nuclear CHOP/GADD153 expression and ultrastructural degeneration of the epithelial cells with intact basement membrane. Pre-treatment of these animals with 4-Phenylbutyrate (1 g/kg/day), before tunicamycin injection, prevented the pathological findings of ATN described above, significantly lowered the tubular injury score and repressed ER stress marker expression. 4-Phenylbutyrate therapy also repressed CHOP/GADD153 expression and normalized Pars Recta ultrastructure. Mechanistic experiments conducted in human proximal tubular cells demonstrated that the tunicamycin-induced ATN response was medicated by CHOP/GADD153. Genetic disruption of CHOP/GADD153 in the C57BL/6 mouse prevented tunicamycin-induced AKI. In conclusion, CHOP/GADD153 appears to be a viable molecular target for the inhibition of AKI. Investigations are ongoing to determine if this result may be generalized to AKI of diverse etiology including ischemia due to chronic heart failure.

Speaker
Biography:

Jean-Claude Dussaule (MD- PhD) is currently Professor of Physiology, University UPMC (Paris VI) and Chief of Division of Physiology, at St-Antoine Hospital, Director of the Medical Pole “Spécialités Médicales” of “Hôpitaux de l’Est Parisien” (Paris, France). He is a member of the Research Unit: UMR702 Inserm-UPMC, and has published more than 110 papers referenced in PubMed. His expertise regarding experimental research is in the fields of renal and vascular endocrinology, renal fibrosis and hemodynamics and hypertension.

Abstract:

The Notch3 receptor is normally expressed in vascular smooth muscle cells and participates in the development and maturation of vessels. Mutations of Notch3 in humans are associated with defective regulation of cerebral blood flow. The role of Notch3 in the regulation of renal hemodynamics was investigated using mice lacking expression of the Notch3 gene (Notch3-/-). The renal vascular resistance of Notch3-/- varied little after exogenous administration of vasoconstrictor or vasodilator agents. Renal resistance microvessels of Notch3-/- showed a deficient contractile response to vasoconstrictors due to a lower entry of extracellular calcium. This abnormal response was attributed to a developmental deficiency of the maturation of VSMC leading to structural heterogeneity in the thickness of the renal vascular wall and the dysfunction of calcium entry channels. In separate studies we found that a de novo activation of expression of Notch3 occurred in the renal epithelium following aggression (UUO and anti-GBM models of nephropathy). This de novo activation initiated phenotype changes making epithelial cells to acquire a pro-inflammatory, pro-migratory phenotype. Notch3-/- or wild type mice treated with antisense oligodeoxynucleotides targeting Notch3 were protected as they exhibited less proteinuria, uremia and inflammatory infiltration. These results show an important and complex role for Notch3 in renal physiopathology. Activation of Notch3 during development contributes to the maturity of resistance vessels and is necessary for the adaptive response of the renal vasculature to vasoactive systems. In contrast, neo-activation of Notch3 in adulthood is detrimental as initiates and contributes to cellular events associated to loss of renal function.

Joshi Shivani

Aarhus University Hospital, Denmark

Title: Mutation spectrum in Danish patients with steroid resistant nephrotic syndrome

Time : 17:15-17:35

Speaker
Biography:

Joshi Shivani was awarded an international mobility PhD scholarship from Aarhus University in 2010 and is currently pursuing a PhD in Translational Molecular Medicine at Aarhus. Her research is focused on studying the mutation spectrum in Danish patients with steroid resistant nephrotic syndrome; identifying new genes in steroid sensitive nephrotic syndrome and using animal models to understand the pathophysiology of nephrotic syndrome. She has presented her work at various national and international conferences. She has won several research grants in connection to her PhD, published a review on genetics of Nephrotic syndrome, is a member of Danish Society of Nephrology and is a Youth Goodwill Ambassador for Denmark.

Abstract:

Variations in genes encoding glomerular proteins like NPHS1, NPHS2 and INF2 have shown to be associated with steroid resistant nephrotic syndrome (SRNS). Patients with genetic forms of SRNS are usually unresponsive to immunosuppressive therapy and are at risk of developing end stage renal disease. Thus, knowing the underlying genetic etiology has important implications in therapeutic decisions. The study aimed to establish a rapid and highly sensitive method for scanning variations in SRNS genes and to determine their spectrum in the Danish patients. Variations in coding regions of NPHS1 and NPHS2 as well as hot spot exons of INF2 were scanned using high-resolution melting analysis and confirmed by bi-directional sequencing in 40 Danish patients diagnosed with sporadic SRNS. This analysis identified some previously described pathogenic variations like c.550G>A in INF2, c.686G>A and c.855_856del in NPHS2 as well as c.349G>A, c.1223G>A, c.3047G>A and c.3230A>G in NPHS1. In both patients and controls we also identified known polymorphisms in NPHS2 and NPHS1. In addition, it was identified that some novel exonic and intronic variants of unkown significance that are predicted to affect splicing of NPHS1 and INF2. Interestingly, while most patients are compound heterozygous for potential pathogenic variations in NPHS1, some have single heterozygous variations in both NPHS1 and NPHS2, respectively. Our results show that 1) high-resolution melting analysis is a rapid and sensitive technique for mutation screening of SRNS genes and 2) the identified variations do explain the occurrence of SRNS in approximately 50% of the patients suggesting further loci heterogeneity in Danish patients with SRNS.

Lydia Benhocine

University Hospital of Beni Messous, Algeria

Title: Cancers, chemotherapies and hemodialysis: A retrospective study

Time : 17:35-17:55

Speaker
Biography:

Lydia Benhocine is MD, and Nephrologist. She received her medical doctorate from Medical School of Algiers in 2003 and completed her Residency in Nephrology with honor as a Assistant Professor in 2008. She worked on pediatric and adult renal transplantation and was trained for transplantation in Clinic Barcelona with Pr Campistol. She is actually Head of Department of Hemodialysis in one of the biggest University Hospitals of Algiers. She has made numerous presentations at national and international scientific meeting and publications in national journals. She is member of the Algerian Society of Nephrology and also representative of North African Region for the Middle East Society for Organ Transplantation (MESOT).

Abstract:

Management of patients with cancer has become almost the same as a chronic disease thanks to the effectiveness steadily improved therapies available in the treatment of cancers. Tolerance and toxicity especially Renal Tolerance and toxicity of these therapies is a major problem and often under estimated. It may be the result of hemodynamic changes, organic lesion and/or blockage of urinary tracks. A study has been made in order to determine the frequency of patients supported in acute hemodialysis for a neoplastic etiology or secondary to a chemotherapy compared to the general population managed in acute hemodialysis. Also, identifying the mechanism involved in this renal disease for these patients and finally assessing the fate of these patients. We have carried out a retrospective study from January 2011 to January 2013 (24 months) at our hemodialysis unit including 237 patients supported for acute hemodialysis, 41 patients had an AKI among them 29 were cancerous. The circumstances of the occurrence of renal failure taken into account are post chemotherapy and induced by the tumor process (compression, flooding) were excluded from the study patients receiving chronic hemodialysis and having developed a neoplasia in a second time. Our results were as follows: 71% of AKI supported during this period were linked to a cancer predominantly female 18w/11m, an average age of 54 years with two cases of pediatric age. The haematological malignancies are particularly providers of kidney damage (48%) in particular the multiple myeloma (MM), followed by uro-genital neoplasia (42%), a higher frequency of MM in women (7W/3M). The tumor lysis syndrome occurs most often during chemotherapy for certain haematological malignancies (lymphoma). The cases of nephrotoxicity found were related to the use of cisplatin and gemcitabine. The evolution of these patients was predominantly bad. Optimization of renal tolerance of cancer chemotherapy pass by an appropriate assessment of renal function of these patients before and during treatment, to each pastor in general but also by the adaptation of doses.

Thoraya Al Maslamani

Hamad Medical Corporation, Qatar

Title: Ritiximub in refractory childhood nephrotic syndrome

Time : 17:55-18:15

Biography:

Thoraya Al Maslamani has completed the PhDs 1997 from King Faisal University of Saudi Arabia. completed Arab Board Pediatric residency program in 2003. She worked in Pediatric Nephrology department at Hamad Medical Hospital in Qatar. in 2008 and finished 2 years of pediatric nephrology fellowship from hospital of sick children Toronto, Canada. Currently working as Pediatric Nephrology consultant at Hamad Medical Corporation, and Assistant Professor of Weill Cornell medical college Qatar.

Abstract:

Idiopathic nephrotic syndrome is one of the most common glomerular disease in children, although most of cases respond to steroid treatment (>80%) approximately 40% develop refractory nephrotic syndrome, these patients usually treated with high dose of steroid in addition to immunosuppressant. As its difficult to use this immunosuppressant’s for long time because of their serious side effects. Ritiximub is a monoclonal antibody directed against the CD20 receptor on B-cells, has been successfully used to treat patients with refractory nephrotic syndrome, and it’s significantly reduce the use of steroid and immunosuppressant. Its considered that ritiximub is relatively well tolerated in children with nephrotic syndrome, with minimal side effect. Still no established regimen dose, some center used single dose of 357mg/m2 some used repeated doses 2-4 in weekly intervals. The aim of this literature review is to asses efficacy and safety of ritiximub in treating childhood refractory nephrotic syndrome, and to review different protocols of ritiximub doses, and its efficacy in long remission.

Speaker
Biography:

Irma Esther Del Moral Espinosa completed her Medical Degree at Anahuac University, Pediatrics at Mexico’s Infantil de México Federico Gómez Hospital and Pediatric Nephrology at the National Pediatrics Institute in Mexico City. She currently leads the nephrology service at the Mexico’s Children’s Hospital Federico Gómez, the leading renal-transplant hospital in Latin America. She was awarded the best published paper from Latin America by the Pediatrics Association of Spain (2011) for the work “Paricalcitol in children with hyperparathyroidism” and the Best Pediatrics Dissertation (2003) “Enuresis associated to allergy”.

Abstract:

Introduction: 5% of children with idiopathic nephrotic syndrome (NS) present steroid-resistant nephrotic syndrome (SRNS) with the presence of focal segmental glomerulosclerosis (FSGS). Objective: Demonstrate treatment with Prednisone (PDN) and Tacrolimus (FK) in pediatric patients with SRNS for a period of 12 months having greater frequency of complete or partial remissions in relation to the standard treatment with prednisone and Cyclosporine (CyA). Material and Methods: Comparative, multicenter randomized clinical trial was conducted in children with SRNS, approved by Investigation and Ethics Committees; both groups received PDN 60 mg/m2/day, during 1 month continued by 30 mg/m2/ day each/48 h. for 5 months. Group I received CyA 5 mg/kg/day in two doses for 12 month. Through levels 100-200 ng/ml. Group II received FK 0.10 mg/Kg/day in two doses for 12 months. Through levels 5-10 ng/ml. renal biopsy at beginning of treatment and control at 12 months. Cholesterol, albumin and serum creatinine, glomerular filtration rate, proteinuria were determinated in both groups. Results: 20 patients were included, 10 in Group I and 10 in Group II with follow-up of 8 years. Response complete 50% (5) for Group I, 80 % (8) for group II, partial response 10% (1) in group I, no response in 10% (1) of each groups. Secondary hypertension was present in 71.42% for group I and 25% for group II. FSFS were present at 90% biopsies for both groups and no statistical changes of nephrotoxicity. Conclusion: In pediatric patients with SRNS, the treatment FK-PDN had a greater percentage of complete remission than CyA-PDN treatment and lower incidence of hypertension and nephrotoxicity.

Muhammad Zain Mehdi

University of Health Sciences, Pakistan

Title: MCM-2 is a better proliferation marker than KI-67 in renal cell carcinomas

Time : 18:35-18:55

Biography:

Muhammad Zain Mehdi after completing his early education acquired MBBS degree from Punjab Medical College, Faisalabad Pakistan and was one of the position holders at the end of the term. He completed his foundation year in the Allied Hospital Faisalabad and joined University of Health Sciences Lahore Pakistan to pursue his Masters of Philosophy in Morbid Anatomy and Histopathology. Currently he is a resident for FRC Path II training at Shaukat Khannum Memorial Cancer Research Hospital Lahore, Pakistan

Abstract:

Introduction/Background: Fuhrman nuclear grade is the most important histological parameter to predict prognosis in a patient of renal cell carcinoma (RCC). However, it suffers inter-observer and intra-observer variation giving rise to need of a parameter that not only correlates with nuclear grade but is also objective and reproducible. Proliferation is the measure of aggressiveness of a tumour and it is strongly correlated with Fuhrman nuclear grade, clinical survival and recurrence in RCC. Ki-67 is conventionally used to assess proliferation. However, renal cell carcinoma has a low proliferating fraction due to which it is unsuitable for routine semi-quantitative analysis. Mini-chromosome maintenance 2 (MCM-2) is a lesser known marker of proliferation and identifies a greater proliferating fraction. This study was designed to assess the labelling index of MCM-2 as compared to Ki-67 by both quantitative and semi-quantitative analysis and to relate this expression with Fuhrman nuclear grade in RCC. Material and Methods: A total of n=50 biopsies of various histological subtypes, grades and stages of RCC were selected from patients of adult age group. Immunohistochemical staining using Ki-67 (MIB-1, Mouse monoclonal antibody, Dako) and MCM-2 (Mouse monoclonal anti-body, Thermo) was performed on the paraffin embedded blocks and labelling indices (LI) were determined by two pathologists independently. Both quantitative and semi-quantitative analyses were performed. Statistical analysis was carried out using SPSS 20.0. Kruskall-Wallis test was used to determine a correlation of proliferation markers with grade and Pearson’s correlate was used to determine correlation between both proliferation markers. Finally, Spearman’s correlate was carried out to determine correlation between quantitative and semi-quantitative analysis for both markers. Results: Labelling index of MCM-2 (median=24.29%) was found to be much higher than Ki-67 (median=13.05%). Both markers were significantly related with histological grades of RCC (p=0.00; Kruskall-Wallis test). LI of MCM-2 was found to correlate significantly with LI of Ki-67 (r=0.0934; p=0.01 with Pearson’s correlate). Semi-quantitative analysis of MCM-2 was found to be accurate even for cases with low proliferative potential (grade I=0.884; p=0.004, Spearman’s correlate) as compared to Ki-67 (grade I=-0.51; p=0.904) which showed no relationship with quantitative analysis in those cases. Conclusion: Both Ki-67 and MCM-2 are markers of proliferation which are closely linked to the tumour histological grade. However, the low proliferation fraction identified by Ki-67 makes its analysis difficult outside a research lab. MCM-2 on the other hand can be used reliably to determine the proliferation fraction of the tumour in a semi-quantitative analysis and thus is an objective and reproducible parameter that can help complement Fuhrman nuclear grade to determine the aggressiveness of the tumour.