Day 1 :
Keynote Forum
Michael F Michelis
Lenox Hill Hospital, USA
Keynote: Kidney: Nephrology and therapeutics
Time : 09:15-09:55
Biography:
Michael F Michelis has been the Director of the Division of Nephrology at Lenox Hill Hospital for more than three decades. He is Professor of Medicine at the Zucker School of Medicine at Hofstra/Northwell. He received a BA at Columbia College, Columbia University in New York City, and his MD at George Washington School of Medicine in Washington, DC. He received his Nephrology Training at the University of Pittsburg, School of Medicine. He has been selected for inclusion in the listing of Top Doctors in New York for the past several years. He is the co-editor of several medical textbooks, and he has published dozens of articles in the area of general nephrology, electrolyte disorders, hypertension, and geriatric renal diseases. He has lectured extensively throughout the United States, Hawaii, Japan, and in various European cities. He has served on the Editorial Board of several medical journals, and he also reviews articles for established journals in Nephrology. He has received many awards and lectureships for his work in nephrology.
Abstract:
Patients with the advanced renal disease have become more complicated and factors such as complex associated conditions, aging, increasing numbers of available pharmacologic agents and improvement in renal replacement therapies have made decision making more challenging. Subjects evaluated include proper approaches to blood pressure therapy in patients with pre, inter or intra dialysis blood pressure abnormalities. Medication characteristics outlined and the effects of various drugs as they relate to the dialysis procedure have been described. Also, metabolic issues such as approaches to hyperuricemia and metabolic acidosis have been reviewed and discussed. New agents and their benefits and limitations noted and present goals of therapy reviewed. Furthermore, the effects of increased body mass and glucose intolerance on survival, as well as possible corrective measures, elucidated. New approaches to glucose control and current blood pressure goals will be discussed. Finally, current approaches to renal replacement therapy will be reviewed and the importance of the timing of interventions and the choice of access and modality will receive consideration. These issues apply particularly to patients of advanced age. Factors influencing such decisions will be presented and critically evaluated.
Keynote Forum
John K Maesaka
NYU Winthrop Hospital, USA
Keynote: The superiority of new algorithm to approach hyponatremia: High prevalence of renal salt wasting without cerebral disease in general medical wards
Time : 09:55-10:35
Biography:
John K Maesaka was born in Hawaii, received degrees from Harvard College and Boston University School of Medicine, did his medical residencies at Barnes-Jewish Hospital at Washington University In St. Louis and Mount Sinai Hospital in New York and renal fellowship at Mount Sinai Hospital. His interest-driven decision to spend 5 years exclusively in the renal physiology laboratory at Mount Sinai Hospital as a renal fellow and member of the faculty proved to be the best investment he made to pursue an academic career in medicine. He was involved in developing colorimetric methods for the determination of uric acid and phosphorus in blood and urine that were applied to studying the transport characteristics of both electrolytes by renal micropuncture techniques in rat kidney. He developed several bioassays to demonstrate the presence of a natriuretic factor in the blood of patients with renal salt wasting and Alzheimer’s disease and more recently identified the elusive natriuretic factor after more than a 25-year pursuit.
Abstract:
Hyponatremia is the most common electrolyte abnormality that is undergoing dramatic changes in terms of its diagnostic approach and clinical outcomes. The approach for more than 50 years has been dominated mainly by the assessment of the volume status of the patient and determinations of urine sodium concentrations (UNa) that exceed 30 to 40mEq/L. This approach has been hampered by a universally agreed inability to accurately assess the volume status of patients by usual clinical criteria and perceived rarity of cerebral/renal salt wasting (C/RSW) among internists. Differentiating SIADH from C/RSW has been difficult because of identical clinical parameters that characterize both syndromes. We have accumulated enough data to identify the various causes of hyponatremia by determining fractional excretion of urate (FEurate) to propose an algorithm to approach hyponatremic conditions. In this algorithm, conditions with low FEurate <4% include extrarenal salt losses with normal kidney function, Addison’s disease, and edematous states such as heart failure, cirrhosis, and nephrosis. Normal FEurate of 4-11% include psychogenic polydipsia and reset osmostat (RO), and increased FEurate > 11% SIADH/hydrochlorothiazide and C/RSW. SIADH can be differentiated from C/RSW by correcting the hyponatremia by any possible means and observing normalization of FEurate in SIADH as compared to being persistently increased in C/RSW. This algorithm greatly simplifies the diagnosis of patients with Addison’s disease and RO. Our report of C/RSW occurring in patients without cerebral disease has led to our proposal to change cerebral to renal salt wasting (RSW). We utilized this algorithm and differences in physiologic response to isotonic saline infusions between SIADH and RSW to evaluate hyponatremic patients from the general medical wards of the hospital. Isotonic saline does not induce excretion of dilute urines or correct the hyponatremia in SIADH as compared to inducing excretion of dilute urines and correction of the hyponatremia in RSW. In 62 hyponatremic patients, 17 (27%) had SIADH, 19 (31%) had RO, 24 (38%) had RSW, 1 due to HCTZ and 1 Addison’s disease. Interestingly, 21 of 24 with RSW had no evidence of cerebral disease and 10 of 24 with RSW had UNa <20mEqL. We conclude that 1. RSW is much more common than is perceived, 2. The term cerebral salt wasting should be changed to RSW 3. RO should be considered a separate entity from SIADH and 4. SIADH needs to be redefined. This new approach proves the ineffectiveness of the volume approach and the limited value of determining UNa, plasma renin, aldosterone or BNP. Lastly, we discuss the evolving identity of a natriuretic factor in RSW and its therapeutic applications.
Keynote Forum
Moro O Salifu
SUNY Downstate Medical Center, USA
Keynote: The role of F11R antagonists in neointimal hyperplasia in dialysis vascular accesses
Time : 10:55-11:25
Biography:
Moro O Salifu is Chair of the Department of Medicine, Chief of the Division of Nephrology and Director of the Kidney Transplant Program at SUNY Downstate. He is board certified in internal medicine, nephrology and certified in transplant nephrology and interventional nephrology. While in residency and Fellowship training, he won annual awards in the basic science category in the Department of Medicine for six consecutive years as well as four consecutive awards from the American College of Physicians. After fellowship training, he was retained by SUNY Downstate as Assistant Professor in 2001. He has directed the nephrology fellowship training program since 2001 and in 2008 assumed the roles of Chief of Nephrology and Director of the Transplant Program, roles that were crucial to the restructuring of the kidney dialysis and transplant programs at Downstate. He is also a fellow of the American College of Physicians. His research interests are CKD disease progression, vascular biology, and kidney transplant outcomes. His work on vascular biology contributed to the discovery, cloning, and sequencing of the human F11 receptor (F11R) gene. The human F11R is located on platelets and on endothelial cells and involved in platelet adhesion to endothelial cells under inflammatory conditions.
Abstract:
Neointimal hyperplasia (NIH) is the proliferation and migration of smooth muscle cells from the media into the intima in response to vessel injury resulting in luminal narrowing. It is initiated by arterial wall damage induced mechanically or by shear stress resulting from high flow, pressure, and turbulence. The damaged endothelium exposures ligands that attract platelets and recruitment of inflammatory cells and release of cytokines (PDGF, TNF, IL1b, FGF, TGFb, etc.), that facilitate vascular smooth muscle cell proliferation and migration. Clinically, NIH may be the primary underlying lesion in vasooclusive diseases such as stenosis observed in artero-venous fistulas, artero-venous grafts and arterial bypass grafts or secondarily associated with the development of atherosclerosis. Although many advances have been made in the primary and secondary prevention of atherosclerosis, including the use of statins and antiplatelet agents, the approach to NIH using several pharmacologic agents have failed largely because none of the agents address the pathophysiology of NIH, which is an entirely different entity from atherosclerosis. Our group was the first to demonstrate the important role of the F11 receptor (F11R)/JAM-A), in human smooth muscle cell (HSMC) proliferation and migration in vitro. We demonstrated that HSMC exposed to three cytokines TNFï¡, INF ï§, and ILï¢ expressed F11R resulting in proliferation and migration. When F11R was partially knocked down using F11R siRNA, HSMC proliferation and migration was abrogated suggesting that inflammation-induced release of cytokines in blood vessels may induce the expression of F11R, which in turn, would cause the migration and proliferation of activated human HSMC into the intimal layer. Utilization of F11R inhibitors, therefore, represents a logical intervention for pharmacologic prevention and regression of NIH. In this presentation, we will explore the role of F11R in the pathogenesis of NIH and F11R inhibitors as potential therapeutic agents.
Keynote Forum
Aruna V Vanikar
GR Doshi and KM Mehta Institute of Kidney Diseases & Research Centre, Dr HL Trivedi Institute of Transplantation Sciences, India
Keynote: Calcineurin inhibitor toxicity in renal transplantation: The good, bad and ugly
Time : 11:25-11:55
Biography:
Aruna Vanikar a Professor and Head, Dept. of Pathology, Lab Medicine, Transfusion Services and Immunohematology, Stem Cell Therapy and Regenerative Medicine, IKDRC-ITS, Ahmedabad. Awards: 1st recognized teacher of Post-Doctorate Renal And Transplant Pathology Course by Indian Academy of Pathologists, pioneer lady scientist of India, etc; 2 patents: adipose-derived mesenchymal stem cells, and insulin-making SC (given away to IKDRC-ITS), >200 publications. Research: immune tolerance, history, and evolution of Indian renal diseases; generation of MSC, Insulin-secreting SC, Neuronal SC, Cardiomyocytes, Hepatocyte-like cells, regulatory cells etc. On editorial board+reviewer for several journals and TTS abstracts. Currently, President of ISRTP.
Abstract:
Calcineurin inhibitors (CNI) cyclosporine (CsA) and Tacrolimus have significantly improved the early outcome of renal transplantation (RT) by reducing the incidence of acute rejections. Toxicity in the form of diabetogenicity, tremors, gastrointestinal disturbances, hyperlipidemia, and hirsutism are known. Acute CNI nephrotoxicity in the form of acute arteriolopathy, tubulopathy with isometric vacuolization and glomerulopathy in the severest form of thrombotic microangiopathy has been recorded at normal blood levels and chronicity in the form of irreversible stripped interstitial fibrosis, tubular atrophy, and associated glomerular loss are known. Our experience with about 5000 RTs in Indian and African patients shows that these races require lower doses of CNI and yet graft function can be maintained. In a 9 year study of 2392 renal allograft biopsies, we have found CNI toxicity in 11.3% biopsies. In a subset of 157 RT patients, we found that with doses of 0.02-0.03 mg/KgBW Tacrolimus, trough levels were 3.6±3 ng /ml in age group <30 years and 6.3±3.9 ng /ml in patients >30 years. With doses of 0.04-0.05 mg/KgBW, trough levels were 4.3±2.1 ng /ml for patients <30 years and 8.4±5.5 ng /ml in patients > 30 years. Tissue toxicity was noted in the majority of the patients with normal trough levels. To conclude, CNI is essential to game winners in early RT however they prove to be losers when used for > 5 years.
- Kidney
Location: Lexington
Chair
Michael F Michelis
Lenox Hill Hospital, USA
Co-Chair
John K Maesaka
NYU Winthrop Hospital, USA
Session Introduction
Grant T Fankhauser
University of Texas Medical Branch, USA
Title: Challenges and opportunities for vascular surgery in native and transplanted kidneys
Time : 11:55-12:25
Biography:
Grant Fankhauser serves as a vascular surgeon on the faculty of the University of Texas Medical Branch. He completed general surgery and vascular surgery training at the Mayo Clinic. He practices all aspects of open vascular and endovascular surgery, including in the treatment of native and transplanted kidneys. He earned master’s degrees in business administration and health administration since joining the faculty. He serves as the director of quality for the surgery department and has research interests in quality, value, and cost-effectiveness. He serves on numerous editorial boards and committees.
Abstract:
Vascular disease is a well-known source of renal insufficiency. Diseases such as atherosclerosis, fibromuscular dysplasia, aneurysms, and polyarteritis nodosa can negatively affect kidney function. Vascular surgeons must be familiar with these diseases, their diagnosis, and treatment options. New diagnostic and treatment options are available but are underutilized in most centers. A review of these diagnostic and treatment options is presented. Vascular surgeons must also be aware of less common renal-vascular problems that may arise such as with transplanted kidneys, renal bypasses, and juxtarenal aortic aneurysms. Vascular surgeons should familiarize themselves with these surgeries, the possible complications, and the long-term renal repercussions. These renal-vascular challenges offer an opportunity to use open surgical and endovascular techniques to rescue threatened kidneys and help preserve long-term renal function. In the setting of end-stage renal disease, vascular surgeons must be aware of the effect of vascular disease on dialysis access in both the venous and arterial systems and have various techniques ready to address them. The diagnostic and therapeutic options of this disease are discussed and a preview of emerging technologies is presented.
Hua Zhou
The Shengjing Hospital of China Medical University, China
Title: The inhibition of renal miR-150 attenuated kidney injury in lupus nephritis by reducing inflammation and fibrosis
Time : 12:25-12:55
Biography:
Hua Zhou completed her MD at China Medical University, PhD at Hamamatsu Medical University in Japan, and postdoctoral works at NIDDK. Prior to returning to China, she had conducted medical research at NIH for 9 years. Currently, she serves as the Vice Director of the Nephrology Department at Hospital of China Medical University, one of the top 20 medical universities in China. She has published 32 papers in prominent nephrology journals and has reached a citation number of 2300+. She also serves as an outstanding committee member of the Chinese Society of Renal Pharmacology and the Chinese Society of Renal Pathology.
Abstract:
We had previously reported that renal miR-150 correlates with chronicity in repeated kidney biopsies from lupus nephritis (LN) patients and that miR-150 agonist upregulates profibrotic and downregulates antifibrotic proteins in human podocyte, tubular, and mesangial cells. This suggests that miR-150 may be a target for treating renal fibrosis. We recently found that circular HLA-C might regulate miR-150 in LN patients with simple class IV. In this study, we subcutaneously injected locked nucleic acid (LNA)-anti-miR-150 (2mg/kg) in fcgr2b-/- mice, which is a spontaneous LN mouse model with different pathological classification. LNA-anti-miR-150 with FAM was seen in kidneys 6hr after injection. Renal miR-150 increased 2-fold in 40-week LN mice. LNA-anti-miR-150 (twice/week for 6-8 weeks) decreased renal miR-150 levels to around 30% of the diseased mice with scrambled LNA injection but did not show any other organ toxicity. Inhibition of renal miR-150 significantly attenuated proteinuria and kidney injury seen on PAS and MASSON. The levels of proinflammatory genes (Il6A, Ifn-γ, Tnf-α) and profibrotic genes (TGF-β, α-smooth muscle antibody, fibronectin) remarkably decrease and the expression of the anti-fibrotic gene (suppressor of cytokine signaling 1) increased. Lastly, we validated miR-150 in renal biopsies from new onset female LN patients with class III to class V (n=18) without treatment of steroid and immunosuppressant. We found renal miR-150 in LN patients increased compared with normal kidney tissue. We conclude that miR-150 inhibition protected LN from progression by downregulating proinflammatory and profibrotic genes and up-regulating anti-fibrotic genes. This suggested that LNA-anti-miR-150 may be a potential agent for treating renal fibrosis.
Geraldo Bezerra da Silva Junior
University of Fortaleza, Brazil
Title: Kidney involvement in tropical diseases and animal poisoning: Highlights from Brazil
Time : 13:55-14:25
Biography:
Geraldo Silva Junior has completed his PhD at the age of 32 years from the Federal University of Ceara (Brazil) in the field of Medical Sciences and postdoctoral studies from the Federal University of Bahia (Brazil) in the field of Public Health and Epidemiology. He is Adjunct Professor at the Medicine School and Graduate Programs (Master and PhD) at the University of Fortaleza (Brazil) and member of the Department of Epidemiology and Prevention of Kidney Disease of the Brazilian Society of Nephrology. He has published more than 100 papers in reputed journals.
Abstract:
Kidney involvement is common in the course of many tropical diseases, which increases its morbidity and mortality. Acute kidney injury (AKI) is part of the classic severe forms of some diseases such as leptospirosis (Weil’s disease), malaria and viral hemorrhagic fevers. Different patterns of glomerular involvement have been described in many tropical diseases, including diffuse proliferative glomerulonephritis, membranoproliferative glomerulonephritis, mesangial proliferative glomerulonephritis, and focal/segmental glomerulosclerosis. Diseases with a chronic pattern, such as leprosy and visceral leishmaniasis, frequently cause glomerulonephritis, including those described above and even less frequent lesions such as amyloidosis and IgA nephropathy. Renal tubular dysfunction has also been described as a consequence of tropical infections. Renal tubular acidosis, for example, is one of the initial manifestations in visceral leishmaniasis, which is usually asymptomatic and can also be found in other infectious diseases. Another important public health problem faced in tropical areas of the globe is animal poisoning. The more common are spider and snakebites, which can complicate with AKI. Recently, new biomarkers for early detection of kidney injury in tropical diseases have been investigated, including neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein-1 (MCP-1), kidney injury molecule-1 (KIM-1), which seem to be promising tools to help Physicians to early detect kidney injury in the setting of tropical diseases and then adopt renal support measures as soon as possible and avoid severe complications such as end-stage renal disease and permanent dialysis need. In this plenary, we present important highlights from research in the field of Tropical Nephrology from Brazil.
Yasin Idweini Saed Matrouk
Al-Bashir Teaching Hospital-Ministry of Health , Jordan
Title: Vesicoureteral reflux endoscopic treatment by using electrocoagulation
Time : 14:25-14:55
Biography:
Yasin Idweini, Senior consultant of Urology-Amman Jordan. He received a medical degree (1976) and specialty in Urology at Barcelona University-Spain (1980). He obtained Jordanian Board of Urology (1998). He obtained his PhD in Urology with graduating Magna Cum Laude (Barcelona University, 2003). He earned (FEBU) in Paris-France (2004). He published his book titled “Tratamiento del Reflujo Vesicoureteral por Electrocoagulation” (2011). He is an examiner in Jordanian and Arab BOARD of Urology. He obtained the World Academic Championship-2018 in Urology(Electrocoagulation)and in Endoscopic Treatment by the International Agency for Standards and Rating and Fellow Directorate of Urology IASR.
Abstract:
Purpose: We reviewed our experience with endoscopic treatment of (VUR) Vesicoureteric Reflux by electrocoagulation; as a simple technique to determine the efficacy and lack of morbidity of this procedure.
Material and methods: From January 1998 to December 2002, 150 patients with vesicoureteric reflux (210 refluxing ureters) underwent 291 endoscopic electrocoagulation in the hemitrigone in order to treat the reflux. The ratio of male to female was 2:8. Age ranged from 2 months to 47 years and median: 7 years. Localization was bilateral 39% Rt. Side 20%, Lt Side 41%. The grade of vesicoureteric reflux ranged from 2 to 5th grade. Secondary reflux was in 18% of the cases.
Results: Good results achieved in 85% of patients, 25% of the patients underwent repeated coagulation (2-3 times). 12% underwent surgical treatment because of the associated abnormalities (paraureteral vesical diverticulum, ectopic ureterocele, posterior urethral valves, ureteral duplication etc.).
Conclusions: Endoscopic treatment of VUR by electrocoagulation is a simple and safe procedure, with less morbidity, and it is cost effective.
Kamal V Kanodia
Dr HL Trivedi Institute of Transplantation Sciences, India
Title: Antibody-mediated rejection in kidney transplantation
Time : 14:55-15:25
Biography:
Kamal Kanodia completed his MD in 1995 from Saurashtra University, India and post-doctoral certificate course (PDCC) in Renal and Transplant Pathology by Indian College of Pathologists in 2003. Currently, he is Professor in Department of Pathology, Laboratory Medicine, Immunohematology, and Transfusion services in Institute of Kidney Diseases and Research Center (IKDRC)-Institute of Transplantation Sciences (ITS), Ahmedabad, India. He has a keen interest in renal and liver transplant pathology. He has 47 publications and serves on editorial board and reviewer in several journals. He has presented several oral and poster presentations at various national and international conferences.
Abstract:
Antibody-mediated rejection (ABMR) is the most common cause of allograft failure. Acute ABMR occurs in ~ 30% of renal allograft biopsies; ~60% of late allograft dysfunctions are due to chronic ABMR. In renal transplants, acute ABMR is characterized by graft dysfunction manifesting over days and results from pre-formed/de novo donor-specific antibodies (DSA). According to revised Banff ’15 classification all three features must be present for diagnosis of acute/active AMR; (1) histologic evidence of acute tissue injury which includes microvascular inflammation (g>0 and/or peritubular capillaritis ([PTC]>0), fibrinoid necrosis/transmural arteritis (v>0), acute thrombotic microangiopathy, or acute tubular injury; (2) linear C4d staining in PTCs (C4d2/C4d3 by immunofluorescence), or C4d>0 by immunohistochemistry [IHC]. For C4d negative lesions, at least moderate microvascular inflammation (g+PTC ≥ 2)/increased expression of endothelial-associated gene transcripts (ENDATs) (3) serologic evidence of DSAs (HLA/non-HLA). For chronic ABMR, the morphologic evidence is transplanted glomerulopathy (TG) (cg>0), PTC basement membrane multilayering (on electron microscopy) and arterial intimal fibrosis of new onset. The cellular and molecular pathways regulating ABMR are still under study. However, evidence suggests B-cell and plasma cell activation results in the generation of DSAs, which bind to human leukocyte antigen (HLA) or non-HLA molecules expressed on endothelial cells within the renal allograft. In our experience of 2316 allograft biopsies from 2008 to 2016, ABMR was seen in 23.6% of patients. Mean HLA was 2.11±1.44 and mean S.Cr. was 2.7±1.45mg/dL.
Khamisa Almokali
King Abdullah Children Specialized Hospital, Riyadh, Saudi Arabia
Title: Carnitine and its role in a patient with renal failure
Time : 15:25-15:55
Biography:
Khamisa Almokali completed her MBBS degree from King Saud University, Saudi Arabia. Then she joined King Abdulaziz Medical City where she finished her pediatric residency program, she has Saudi Board and as well Arab board in Pediatric. In 2010 she joined Sick Kid Hospital, Toronto, Canda to do 3 years pediatric nephrology fellowship program. And currently working as pediatric nephrology consultant at King Abdullah Children Specialized Hospital, Riyadh, Saudi Arabia. As well she is the program director of the pediatric nephrology fellowship. She joined Harvard medical school training program for introduction of clinical research from December 2016 till May 2017.
Abstract:
Carnitine is an important intermediary in fat metabolism. Carnitine deficiency may be a significant problem in a patient with kidney disease, especially those who are requiring maintenance dialysis. In hemodialysis patient, total plasma carnitine level is elevated with reduced free carnitine concentration and the ratio of acyl to free carnitine is markedly increased compared to healthy controls, carnitine deficiency in dialysis patient might cause significant side effects such as cardiomyopathy, intradialytic hypotension, and muscle weakness. Supplementation in such cases is required with good response. The national kidney foundation-kidney disease outcomes quality initiative (NKF-KDOQI) working group developed guidelines for the nutrition in chronic kidney disease including carnitine supplementation.
Bogdan Dima
Cliniques de l’Europe – Hôpital “Sainte Elisabethâ€, Belgium
Title: Vesico-Ureteral Reflux between the paediatric nephrologist and the surgeon
Time : 16:15-16:45
Biography:
Bogdan Dima has completed his medical studies in Bucharest, Romania at “Carol Davila” University of Medicine and Pharmacy. He worked as a Medical Resident and as a Specialised Paediatrician in the Department of Paediatric Nephrology and Dialysis at Fundeni Clinical Institute (Bucharest, Romania) before moving to France in 2009. He attended the Inter-Universities Paediatric Nephrology Course in France (Paris, Nice, Lyon, and Montpellier). Since 2011 he is living and working in Belgium (from 2011 until 2016 in Charleroi University Hospital, and since 2016 in Cliniques de l’Europe in Brussels in the Paediatrics and Neonatology Department).
Abstract:
Throughout the last decades, there were different approaches to the management of the Vesico-Ureteral Reflux (VUR), varying from a conservative medical to an “aggressive”, surgical way. The use of different monitoring and therapeutical methods made the results difficult to compare. In the last years though, thanks to the statistical analysis of various studies results, a more integrated approach emerged. The author of this presentation is sharing his experience with the follow up of the children presenting congenital VUR, focusing on the role of the radiology investigations and of renal scintigraphy in determining the adequate management approach for each child. The conclusions drawn are seen as a base for a debate meant to harmonize the management of the children diagnosed at birth with VUR.
Umang G Thakkar
Dr HL Trivedi Institute of Transplantation Sciences, India
Title: Stem cell therapy for glomerular diseases
Time : 16:45-17:15
Biography:
Umang G Thakkar got his DCH (Paediatrics) from India and has > 10-years’ experience in the field of regenerative medicine. Currently, he is working as an Associate Professor at IKDRC-ITS, Ahmedabad, India. His research interests are stem cell therapy for various disorders, pediatrics. He has >40 publications in various medical journals. He is included as an editorial board member in various journals and a reviewer also. He also received the Government Scholarship and distinguished Awards in the past. He was granted a Young Investigator Award in TTS 2016 at Hong Kong, for his research paper.
Abstract:
Stem cell therapy (SCT) has the potential to develop a novel therapeutic approach to glomerular diseases (GDs). The main goal of SCT is to achieve and sustain the recovery of altered renal functions. We present our preliminary experience of allogeneic SCT included adipose-derived mesenchymal stem cell (AD-MSC) and hematopoietic stem cells (HSC) for GDs. This was IRB approved non-randomized open-labeled prospective clinical study included 8-volunteer GDs’ patients with their informed consent subjected to allogeneic SCT from May,’13 to December,’17. Volunteer donors from blood-related family members were subjected to adipose tissue resection and BM aspiration for in vitro generation of AD-MSC and HSC respectively. Patients were diagnosed with GDs and confirmed by renal biopsy. Primary FSGS was noted in 4, LN in 2, and primary IgAN and MePGN in 1 patient each. In vitro generated SCs were infused via femoral catheterization under local anesthesia into bilateral renal arteries, portal circulation, and thymus (by IITV guidance), with the mean cell volume of 70ml, 30ml, and 3ml respectively, under conditioning of Bortezomib and subtotal lymphoid irradiation. Infused mean MSC count was 34.89x104 cells/KgBW and HSC count was 4.97x108 cells/KgBW with mean CD34+/CD90+/CD73+ of 0.82%, 38.9% and 21.1% respectively. SCT was safe and uneventful. Over mean follow-up of 31.38 months, there was sustained reduction in mean 24-hours proteinuria from 1.356 to 0.45gm/day, decreased SCr from 1.14 to 0.78mg/dL and increased S.alb to 3.68gm/dL with improvement in creatinine clearance and eGFR. Thus, Co-infusion of AD-MSC + HSC offers safe, viable approach to achieve remission in GDs.
Beishebaeva Nasira
National Center of Cardiology and Therapy, Kyrgyzstan
Title: Clinical evaluation of diastolic dysfunction of the left ventricle depending in different morphologic forms of glomerulopathies
Time : 17:15-17:45
Biography:
Beishebaeva Nasira Adylbekovna completed her PhD of Medical Sciences in the year 2004; on the theme “Duration of children’s glomerulonephritis in combination with HBV-infection in Kyrgyzstan.” She did her post-graduation studies during 1998–2002 in pediatric nephrology. She is the Head of the nephrology department, NCMCHP of the Ministry of Healthcare of the Kyrgyz Republic, Kyrgyzstan.
Abstract:
Purpose: Assess the diastolic dysfunction (DD) of the heart with different forms of glomerulopathies (GP).
Materials and Methods: 55 patients with GP were examined (32 men, 23 women) aged from 17 to 58 years (on the average 32.76±10.3). All patients carried out kidney biopsy. IgA, IgG and IgM GP were diagnosed.
Results: The disease debuted at a young age of over 17 years in most patients (78.1%). Clinically, most often there was a nephrotic syndrome (in 65.4%), and in most cases - in men (72.2%). Systolic and diastolic blood pressure was 130.3±20.0 mm Hg. Art and 83.2±13.06 mm Hg. art., respectively. By the nature of the immune deposits with different morphological types of GP, we divided them into three subgroups. In the course of the analysis, the highest value of blood pressure was found in patients with IgG and IgM deposits (138.3±21.6 mm Hg and 136.0±21.0 mm Hg, respectively), so there is a reason to believe, that the formed immune complexes are a factor of endothelial damage. In the study of clinical data, statistically significant differences between groups of patients were revealed. DD was diagnosed in 36.4% of patients with heart failure in the early stages of the disease, before the development of renal failure. The main differences between cohorts were a significant elongation of the isovolumic relaxation time (IVRT) in the group with IgM nephropathy (P<0.005). However, a significant difference in late diastolic movement of the medial part of the mitral ring [A'] (P<0.04) was observed only in the group of patients with IgM nephropathy.
Conclusion: Left ventricular diastolic dysfunction was diagnosed in each third patient with GP in the onset of the disease, without renal failure. The most pronounced signs of diastolic filling identified in patients with IgM nephropathy, as evidenced by the significant differences between groups.
Jagdish Kanagaraj
Meenakshi Hospital, India
Title: Effect of double filtration plasmapheresis on plasma components in varied renal diseases
Time : 17:45-18:15
Biography:
Jagdish Kanagaraj has completed him under graduation (MBBS) from Pondicherry Institute of Medical Sciences (in 2009). He has received medal of honor in Internal Medicine. He pursued his masters in internal medicine in Government Stanley Medical College in Chennai and completed his course in 2013 with medal of honor in internal medicine. His special area of interest includes glomerulonephritis, transplantation in all sensitized individuals and post-transplant infections. He completed his masters in Nephrology in 2017 in Christian medical college, Vellore and was awarded with JCM Shastry award for the year 2017. He has two publications and he is a reviewer in Indian journal of nephrology and international journal of nephrology and Endourology. He is currently working as consultant nephrologist and transplant physician in Meenakshi hospital in Tanjore, Tamil Nadu, India.
Abstract:
Plasmapheresis is a life-saving procedure that either is a treatment modality or a stop-gap procedure to buy time till immunosuppression acts. Unfortunately it removes necessary vital plasma components including immunoglobulins, albumin and coagulation factors. Various selective plasmapheresis options exist. One such is double filtration plasmapheresis which can selectively remove certain component of immunoglobulins. In our experience, with a small prospective observational cohort study, cumulative immunoglobulin removal in various renal indications was as follows-IgG is 72% which is suboptimal, whereas IgA and IgM cumulative removal were 89% and 96% respectively. We also observed effluent fluid albumin concentration will be more physiological way of replacement and serum fibrinogen values less than 50mg/dl resulted in spontaneous bleeding.
- Nephrology
Location: Lexington
Chair
Michael S Goligorsky
New York Medical College, USA
Co-Chair
Mariana Markell
SUNY Downstate Medical Center, USA
Session Introduction
Deepika Jain
New Jersey Kidney Care, USA
Title: Impact of health literacy in dialysis and chronic kidney diseases: Prevalence and outcomes
Time : 10:55-11:25
Biography:
Deepika Jain has completed her MD in New Delhi, India and continued her career in internal medicine and nephrology in the USA at University of Pittsburgh Medical center. She is currently working in the New Jersey as part of New Jersey Kidney Care group. She has published several papers on health literacy on dialysis patients.
Abstract:
Health literacy is the capacity of an individual to understand information related to a disease in order to make an informed decision. In patients with kidney diseases, studies have reported increasing impact of limited health literacy on health outcomes. Our paper discusses current literature on health literacy in kidney diseases.
Health literacy is an increasing recognized cause of suboptimal care and management of chronic diseases in patients. Our paper reviews the current literature on its prevalence and impact in the population with kidney diseases. More studies are needed in patients with kidney diseases to better understand the effect of limited health literacy.
Muthu Jayaraman
Bharathi Rajah Super Specialty Hospital, India
Title: Renal problems in elderly
Time : 11:25-11:55
Biography:
Muthu Jayaraman completed MBBS, MD (Int. Medicine), DM (Nephrology). She is a Gold Medalist in Anatomy and Surgery. Presently, she is a Senior Consultant Nephrologist, Bharathi Rajah Super Specialty Hospital, Chennai. She published Twenty five Papers in Journals and Textbooks, Forty-Two papers presented at National and Inter National Conferences and Twenty Seven Guest Lectures Given in state and national conferences. She is a member of API, Indian Society of Nephrology, ISN Executive Committee and Member Advisory Board of Editorial Board of Journal of ISN.
Abstract:
Aging is a programmed biological process associated with a small transcriptional difference in many genes. It is also called ‘senescence’ which means ‘irreversible growth arrest’. Cellular or replicative senescence is the key element of aging. Aging plays an active role in fibrogenesis and atrophy of renal tissue. The discussing topics includes:
Common renal disorders in the elderly: CKD: Over 60% of the elderly have a GFR less than 60ml/min. However, the serum creatinine is not altered and is stable around 1mg%. In differentiating aging vs CKD, the context is more important. Regardless of age, if the GFR is less than 45ml/mt, with albuminuria of 50-500 mg per day for more than 3 months, it is labeled as CKD.
Hypertension: The optimum BP in the elderly remains uncertain. Studies have shown that aggressive control of BP may lead to hypotension, syncope, acute kidney injury, hypokalemia, and hyponatremia. The consensus is to keep systolic BP, less than 140mmHg and never less than 120mmHg.
Acute Kidney Injury: Acute Kidney Injury (AKI) is a common clinical problem in the elderly. Numerous factors like age-related low GFR, associated comorbid conditions, the risk of dehydration due to lack of thirst, inadequate handling of sodium and water by the aging kidneys, urinary tract obstruction, bladder dysfunction, retention of urine, and poly-pharmacy predispose to AKI.
(RRT) for Elderly: Age is not a limitation for dialysis and the number of patients getting dialysis beyond the age of 75 is increasing. Vascular access like AVF, Vascular graft, and Central venous catheterization can be used in these patients. The risks are an infection, the maturity of AV fistula, early closure, hypotension, and hypoglycemia.
Transplantation for elderly: Number of candidates above the age of 65 years listed for Transplant is very low. Although the survival of elderly after transplantation is favorable, non-availability of donor kidneys, priority given to a younger individual and co-morbidities in the elderly restrict their selection from the pool of potential recipients. Although rejection is less common in the elderly, coronary artery disease and infection account for the higher mortality.
Sergio Wyton L Pinto
Hospital Sao Joao de Deus, Brazil
Title: Ten-year follow-up of patients with epidemic post-infectious glomerulonephritis
Time : 11:55-12:25
Biography:
Sergio Wyton L Pinto is working in the division of nephrology, Hospital Sao Joao de Deus, Divinopolis, Brazil.He has published several articles in the international journals.
Abstract:
Background: Scarce information on outcomes of epidemic post infectious glomerulonephritis is available. This is a 10-year follow-up of the patients that developed acute glomerulonephritis in an epidemic outbreak caused by group C Streptococcus zooepidemicus in Brazil in 1998 that were also previously evaluated 2 and 5 years after the acute episode.
Methods: In this prospective study 60 cases (out of 134 in 1998) were reevaluated after 10 years, as well as community controls matched by gender and age. They underwent clinical and renal function evaluation, including serum creatinine and cystatin C, estimated glomerular filtration rate (eGFR), albuminuria and hematuria.
Results: Comparisons of clinical and renal function aspects of 60 patients and 48 community controls have not shown significant differences (eGFR <60 ml/min/1.73m2 and/or albuminuria >30mg/g creatinine: 13.8% vs. 12.2%, respectively, p=0.817) except for a higher frequency of hypertension in the cases (45.0% vs. 20.8%, p=0.009). Comparing the same patients affected in the acute episode, 2, 5 and 10 years later, it was observed an improvement of median eGFR levels at 2 years and a trend toward subsequent stabilization in these levels, associated with a decrease in albuminuria and increased hypertension rates in the last survey. At 10 years it was not observed an additional reduction of renal function using serum creatinine, eGFR, and Cystatin C.
Conclusion: During the acute episode of epidemic GN a considerable proportion of patients presented hypertension and reduced renal function; after 2 years and particularly at this 10-year follow-up survey there was no worsening of renal function parameters, except for persistent higher frequency of hypertension. Nevertheless, a longer follow up is necessary to confirm that progressive loss of renal function will not occur.
Padmanabhan Subramanian
NU Hospitals, India
Title: Post-transplant erythrocytosis
Time : 12:25-12:55
Biography:
Padmanabhan Subramanian completed his DM in Nephrology from the All India Institute of Medical Sciences, New Delhi, India. He did his MBBS from Madurai Medical College Madurai and DNB in Internal Medicine from Southern Railway Head Quarters Hospital Hospital, Chennai. He was awarded the ISPD Fellowship in October 2003 and he trained under Late Dr DG Oreopoulos in Toronto Western Hospital, Toronto, Ontario, Canada. He did Postdoctoral Fellowship in Renal Medicine at the Singapore General Hospital, Singapore and was the Staff Nephrologist at the National Kidney Foundation Singapore before returning back to India. He is currently the Senior Consultant Nephrologist and Incharge of the Renal Transplant Program at NU Hospitals, Bengaluru, India. He has published over 30 papers in reputed journals. He is a peer reviewer for reputed journals. He is serving as the Executive council Member of the Southern Chapter of India Society of Nephrology.
Abstract:
The factors that contribute to the correction of anemia of Chronic Kidney Disease (CKD) after successful renal transplantation include the production of erythropoietin (EPO) from the allograft and elimination for bonemarrow inhibitors which are present in the uremic milieu. Usually, anemia gets corrected by the 3rd post-transplant month. About 20% of the renal allograft recipients develop persistent high hematocrit of over 51%, a condition termed as post-transplant erythrocytosis (PTE). The pathogenesis of PTE is yet to be fully understood. A quarter of them remits spontaneously within 2 years while in others it persists for many years. Male sex, retention of native kidneys, transplant renal artery stenosis and a normal graft function are some of the predisposing factors for the development of PTE. Thromboembolic events occur in about 10-30% of those with PTE. The mortality rate is very less. Use of ACE inhibitors is a safe and well-tolerated treatment for PTE. Therapeutic phlebotomy is usually done when the hematocrit crosses 55% and is very effective. At NU hospitals, we had an unusually high incidence of PTE (26%). Fortunately, none were symptomatic.
Maria Celeste RÃos
Hospital Carlos G Durand, Argentina
Title: Amyloidosis with peritoneal involvement, continuous ambulatory peritoneal dialysis: A case report
Time : 13:55-14:25
Biography:
Maria Celeste Ríos obtained her medical degree at the Buenos Aires University of Medicine (UBA). Later, she got her specialty in general medicine at the Central Aeronautical Hospital, where she was a chief resident for one year. She has recently finished her postgraduate studies in Nephrology at the Carlos G. Durand Hospital, along with the postgraduate course in Nephrology at the Buenos Aires University of Medicine. She has participated in multiple national conferences as a speaker, exposing different works made during my academic training in Nephrology. She is currently working as a staff nephrologist at the Deutsches Hospital in Buenos Aires.
Abstract:
Amyloidosis is a systemic disease characterized by the extracellular deposition of amorphous fibrillar protein, which leads to the loss of the function of the affected organ. Renal involvement is a common case expressed as nephrotic syndrome with varying degrees of functional deterioration, until a final stage in which renal replacement therapy is required. In the same way, the gastrointestinal tract is affected by the amyloid deposits, which are located mainly around the arterioles and in muscles causing ischemia and eventually, leading to mucosal erosion. However, peritoneal secondary amyloidosis (AA amyloidosis) is unusual. In our bibliographic search, there are no records or data related to patients with peritoneal AA amyloidosis undergoing continuous ambulatory peritoneal dialysis (CAPD) in whose procedure the peritoneum is used as a dialysis membrane. We therefore hereby describe the case of a patient with a history of pulmonary tuberculosis diagnosed in 2001 with reactivations in 2005 and 2011, with complete treatment that evolves with nephrotic syndrome and CKD stage V. The histological diagnosis was: renal and peritoneal AA amyloidosis. Because of the requirement of renal replacement, our patient started with positive selection, continuous ambulatory peritoneal dialysis (CAPD). We stand out that despite presenting peritoneal amyloidosis; the peritoneum could be used as dialysis membrane over 3 years. Moreover, our patient had a satisfactory quality of life, maintaining values of hematocrit, adequate mineral-bone metabolism and improvement of values of albumin along the therapeutic, as well as adequate control of urea levels and preserving residual renal function.
Murkamilov Ilkhom Torobekovich
I.K. Akhunbaev Kyrgyz State Medical Academy, Kyrgyzstan
Title: Cystatin C: As a biomarker of cerebrovascular diseases in renal dysfunction
Time : 14:25-14:55
Biography:
Murkamilov Ilkhom Torobekovich was born in the Osh region of the Karasuisky district in 1983 on April 22. He received his higher professional education in the KSMA named after I.K. Akhunbaeva. Candidate dissertation is devoted to the topic "The influence of erythropoietin and the combination of erythropoietin with hypoxic pressure chamber training on anemia in chronic glomerulonephritis. (2016). More than 20 scientific publications on the problems of clinical nephrology have been published. At the moment, a doctoral student at the KRSU named after B.N. Yeltsin at the Department of Therapy No.2 specialty "Medical Business". Research topic: Chronic kidney disease and cerebrovascular disease. He is the chairman of the Society of Specialists on Chronic Kidney Disease in Kyrgyzstan.
Abstract:
The prevalence of chronic kidney disease (CKD) in recent years growing in many countries of the world, accounting for more than 10% of the total population, and among persons, the frequency of CKD is significantly higher in older age groups. In the last time, the problem of kidney dysfunction and associated cerebrovascular diseases (CVD) becomes very relevant. The most important and complex aspects of this problems are the inhibition of progression of both CVD and renal dysfunction. Numerous studies show that in CKD, the risk of vascular complications increases even at the pre-dialysis stage of the disease. Exactly vascular events, not progressive deterioration of kidney function-the most frequent cause of death the patients with CKD. It is known that the most common variant structural changes in the arteries of CKD is atherosclerotic lesion carotid arteries (CA). In this study, the thickness of the intima-media complex (TIM) with the help of B-mode ultrasound (ultrasound) with an assessment of carotid plaque is currently a recognized surrogate marker of atherosclerosis, frequency, and severity of which in CKD depends on the value of the glomerular filtration rate (GFR). Atherosclerosis CA-an indispensable element in the pathogenesis of cerebrovascular and renal diseases, considered as a factor, it contributes to the further progression of these pathologies. Lately the possibility of using as a laboratory predictor Atherosclerosis CA and CVD Cystatin C-one of the renal biomarkers. The main aim was to study the role of cystatin C as a biomarker of atherosclerotic lesions of carotid arteries and cerebrovascular diseases in patients with a therapeutic profile.
Conclusion: An increase in the content of cystatin C is associated with an increase in the level of systolic and central blood pressure, calcium and cholesterol of the blood plasma, as well as with thickening of TIM.
Kamlesh S Suthar
Dr HL Trivedi Institute of Transplantation Sciences, India
Title: Anti-PLA2R antibody in membranous nephropathy: How useful is it
Time : 14:55-15:25
Biography:
Kamlesh Suthar completed his MD in 2006 from Gujarat University, India. He qualified with a post-doctoral certificate course (PDCC) of Renal and Transplant Pathology (Indian College of Pathologists) in 2009 and has >10-years experience in the field. Currently, he is Associate Professor in the Department of Pathology, Laboratory Medicine, Immunohematology, and Transfusion services at IKDRC-ITS, Ahmedabad, India. He has >30 publications, several oral and poster presentations at national and international conferences. He serves as reviewer and editorial board member of various journals. He received “Young Investigator Award” in “Transplant Update-2015” for his research on BKV nephropathy in renal transplantation.
Abstract:
Membranous nephropathy (MN) is the commonest cause of nephrotic syndrome in adults, with male preponderance. Immunosuppressive agents are the main treatment. However, ≈40% patients progress to end-stage renal disease and ≈15% develop recurrence post-renal transplantation. It is important to differentiate MN in to primary/ idiopathic (pMN) and secondary (sMN) type since their treatment and prognosis are different. Morphologically it can be differentiated with the aid of light, immunofluorescence (IF) and electron microscopy. Antibody against M-Type Phospholipase A2 Receptor (anti-PLA2R) which is the target antigen present in the glomerular basement membrane is commonly associated with pMN. PLA2R antigen in glomerulus can be located by through IF/immunohistochemistry (IHC). Renal biopsy is an invasive procedure, hence non-invasive biomarkers like the anti-PLA2R antibody in serum can be helpful and preferable to differentiate and monitor pMN vs sMN. It can be detected in serum by various assays like western blot, indirect immunofluorescence (IIF) -Cell-based assay and enzyme-linked immunosorbent assay (ELISA). Each method has its own advantages and limitations. ELISA is commonly used assay with 70-75% sensitivity and >95% specificity. Our experience of 70 patients has shown that anti-PLA2R antibody by ELISA may be positive in both pMN as well as sMN with 39.13% sensitivity. Negative anti- PLA2R antibody titer does not exclude the possibility of primary or idiopathic MN and such cases require further evaluation. Larger sample size with follow-up would be required to establish the role of anti- PLA2R antibody titer as a prognosticator in MN.
Gorana Nedin Rankovic
University of Niš, Serbia
Title: Polypharmacy in elderly patients with chronic kidney failure and its association with potentially inappropriate prescribing of drugs
Time : 15:25-15:55
Biography:
Gorana Nedin Rankovic was born on September 18th, 1985 in Nis, where she finished her primary and high school with great success. She enrolled Medical Faculty in Nis in 2003 and graduated in 2009. In 2009 she enrolled Doctoral Academic Studies at the Medical Faculty in Nis. By the Teaching Scientific Council of the Medical Faculty in Niš, she got her PhD thesis approved under the title "Analysis of factors that influence the rational prescription of drugs in elderly patients with renal insufficiency". In 2012 she enrolled Specialistic Academic Studies, Clinical Pharmacology. In October 2012 she started working as a teaching associate at the Department of Pharmacology and Toxicology, Medical Faculty in Niš, and in October 2015 she was selected as teaching assistant at the same Department. During her professional career, she was the author and co-author of twenty-five (25) scientific papers printed in domestic and international journals. She is one of the authors of the book "Physiology with Physiology of Sport". She is a member of the Serbian Pharmacology Society and a member of the Clinical Pharmacology section of Serbia.
Abstract:
Introduction: Given that the number of people over 65 years of age is increasing worldwide, polypharmacy is becoming more and more present in the elderly. Unfortunately, polypharmacy can be associated with many negative outcomes, such as higher costs of treatment, both for the patient and the health care system in general, due to the increased use of health care, increased risk of drug-related adverse events, no adherence to therapy due to the numerous medications that the patient takes, drug interactions, etc.
Purpose: The aim of this study was to determine the prevalence of polypharmacy in elderly patients with chronic kidney failure (CKF), and also to explore if it affects the occurrence of potentially inappropriate prescribing (PIP) of drugs.
Methods: The study was based on a cross-sectional design, and it was conducted at the Department of Nephrology, Clinical Center in Nis. Criteria for inclusion in the study were: age of 65 years and more, written consent for participation in the study, and the presence of chronic kidney failure The data were collected from the interviews with patients, as well as from medical files. The presence or absence of inappropriate drug prescription was determined by two explicit criteria Beers and STOPP.
Results: The study included 135 patients aged 65 years and over with varying degrees of CKF, whereby the majority of patients (34.9%) had the third stage of CKF. 78 (57.78%) patients were men and 57 (42.22%) were women. The average number of prescribed drugs was 7,13±2,61 (maximum 16). According to the Beers criteria, PIP was found in 44 (32.6%) patients, while 55 (40.7%) patients experienced PIP according to the STOPP criteria. A major factor associated with PIP by both criteria was polypharmacy. Each additional drug increased the risk of PIP according to Beers criteria 1.6 times (p<0.001).
Conclusion: Although polypharmacy paradoxically connects with poorer treatment, it is first necessary to estimate the overall quality of the prescribed drugs and not only the total number of medications taken by the patient.
Mangal Charan Murmu
SCB Medical College, India
Title: Use of dialysis in acute kidney injury in pediatrics
Time : 16:15-16:45
Biography:
Mangal Charan Murmu (Age: 44yrs) completed his MBBS (1991-97) from MKCG Medical College, Berhampur and he obtains his MD (Pediatrics-1999-2002) from VSS Medical College, Burla, Sambalpur. Now he is working as Associate Professor in SCB Medical College, Cuttack, Odisha, India. He has got 5 international, 15 national and 20 state publications. He is the examiner of both Undergraduate & Postgraduate for West Bengal Health University, Chhattisgarh Health University, Andhra Health University, Manipur Health University.
Abstract:
Aim: To study the use of Dialysis in Acute Kidney Injury (AKI) in different clinical conditions in pediatric practice in a tertiary care hospital.
Method: It’s a direct prospective study done in the Paediatric Department of SCB Medical College, Cuttack, Odisha, India. The child admitted with a clinical feature of AKI was taken into study. Total numbers of cases taken in the study from January 2015 to December 2017 were 48. AKI due to severe malaria (n=18), septicaemia (n=14), vasculotoxic snake bite (n=8), severe dehydration (n=6), complicated urinary tract infection (n=2) were included. The data obtained were analyzed and statistically validated.
Results: Prerenal was the most common cause of AKI needing dialysis.
Conclusion: The dialysis done in the early phase of clinical condition reduces the mortality due to ARF.