Kidney Week Late-Breaking Clinical Studies Highlight Advances in Kidney Care

EMBARGOED FOR RELEASE UNTIL NOVEMBER 7 AT 12:30 PM EST (9:30 AM PST)CONTACTS: Kurtis Pivert • [email protected] • 202-699-0238Bob Henkel • [email protected] • 202-557-8360ASN KIDNEY WEEK 2015 • NOVEMBER 3–8 • SAN DIEGO, CA

KIDNEY WEEK LATE-BREAKING CLINICAL STUDIES HIGHLIGHT ADVANCES IN KIDNEY CAREWearable artificial kidney trial results among clinical advances being presented

Newswise — San Diego, CA (November 7, 2015) — The results of numerous high-impact clinical trials that could affect kidney-related medical care will be presented at ASN Kidney Week 2015 November 3–8 at the San Diego Convention Center in San Diego, CA.

Among the studies are the following (presented in numerical order):

SA-O1092 Nephrotoxicity of Invasive and Noninvasive Coronary Angiography: Randomized Controlled Study of Intracoronary and Intravenous Contrast Agent Administration — Eva Schönenberger, Patricia D. Bady, Peter Martus, Elke Zimmermann, Michael Laule, Marc Dewey. Berlin, Germany.

Acute kidney injury can be induced by contrast agents used for X-ray examinations. Invasive X-ray angiography is the standard test for the diagnosis of blocked coronary arteries (coronary disease). Among the alternative diagnostic tests, computed tomography (CT) - a noninvasive X-ray examination – has the highest accuracy for detecting coronary disease. Whether invasive angiography or noninvasive CT poses a greater risk for acute kidney injury is unknown.

We performed a randomized study in which patients with suspected coronary disease underwent either invasive angiography or CT. The same X-ray contrast agent was used for these two procedures and was given directly into the coronary arteries for angiography or into superficial veins for CT. We found that acute kidney injury was about two to three times more likely when invasive angiography was performed as compared with CT. The diagnosis of coronary disease by CT may thus offer two advantages: noninvasiveness and at the same time reduced risk of kidney injury.

SA-PO1094 Low Osmolar Diet and Adjusted Water Intake for Vasopressin Suppression in ADPKD: A Randomized Controlled Trial — Osama W. Amro, Jessica K. Paulus, Farzad Noubary, Ronald D. Perrone. Boston, MA.

Vasopressin is the hormone responsible for water regulation in our body. High vasopressin has been linked to many diseases including high blood pressure, heart and kidney diseases in general, and autosomal dominant polycystic kidney disease (ADPKD) in particular. It is known that a high fluid intake can reduce vasopressin. However, adherence to a high fluid intake is difficult for patients to maintain in real life. To address the challenges associated with a high fluid intake, we developed and tested a novel dietary intervention that lowers the amount of water needed to suppress vasopressin. In this randomized controlled trial conducted at Tufts Medical Center in 34 patients with ADPKD, we showed for the first time that a diet-based intervention can lower vasopressin, and reduces the amount of water patients need to drink to achieve vasopression reduction. This intervention is based on a stepwise approach of combining a diet low in protein and salt (low osmolar diet) with individualized adjusted water intake based on a patient’s salt and protein consumption. This intervention offers a safe, easily-tolerated and affordable approach that can be adopted in the early stages of ADPKD to prevent permanent kidney damage and slow cyst progression. The trial has tremendous public health relevance, given the large numbers of people affected by ADPKD, and lack of treatments that prevent development of end stage renal disease. In addition, this novel dietary intervention has the potential to be investigated and applied to management of other kidney and cardiovascular diseases.

SA-PO1097 Corticosteroid Monotherapy versus Combined Immunosuppression in IgA Nephropathy: Insights from the STOP-IgAN Trial — Jürgen Floege, Thomas Rauen, Frank Eitner, Christina Fitzner, Ralf-Dieter Hilgers. Aachen, Germany.

IgA-nephropathy (IgAN) is the most common immune disease of the kidneys in Western countries. It affects mostly young adults, is often a chance finding since the disease causes few symptoms, and it can lead to end-stage kidney failure in up to 20% of affected individuals. In fact, IgAN is the most frequent cause of end-stage renal failure in young adults in many countries worldwide. Although the disease is considered to be mediated by a dysfunction of the immune system, evidence that suppression of the immune system, for example with corticosteroids or cytotoxic drugs such as cyclophosphamide, is effective in treating high risk patients with IgAN, is weak. We performed one of the largest trials in IgAN in various nephrology centers in Germany. We first optimized “simple” measures like blood pressure control and measures to reduce protein loss by the kidneys (so-called “supportive therapy”) and then only randomized those patients who remained at a high risk for kidney failure to either continue on supportive therapy only or to receive additional immunosuppression. Our data clearly show that the addition of immunosuppression does not improve the preservation of kidney function beyond that achieved with a comprehensive supportive care approach. Instead, adverse effects increased significantly with immunosuppression and we even had one patient die from an infectious complication during cyclophosphamide medication. Taken together, our trial casts doubt on the value to two commonly employed immunosuppressive regimens (one with corticosteroids only, one with combined corticosteroid-cyclophosphamide-azathioprine therapy) once all supportive care measures have been optimized.

SA-PO1099 Establishing Endpoints for Lupus Nephritis Clinical Trials: Progress by the Kidney Health Initiative/Lupus Nephritis Trials Network Collaboration — Brad H. Rovin, Meggan Mackay, Joanna Stein, Maria Dall’Era, Kenneth Kalunian, Martin L. Lesser, Melissa West. Columbus, OH.

The kidney disease that is seen in patients with systemic lupus erythematosus (SLE) is called lupus nephritis. It is a very severe manifestation of SLE and occurs in about half of the patients. Lupus nephritis is associated with increased morbidity and mortality in SLE patients, and not infrequently results in chronic kidney disease or end-stage kidney disease requiring dialysis or transplantation. Treatments for lupus nephritis are highly toxic immunosuppressive agents, and many patients do not completely respond to these medications. Several new therapies have been tested for lupus nephritis, many with the potential of being more effective and less toxic than standard-of-care. However, none of those trials convincingly demonstrated that the new therapies were effective.

A big problem with lupus nephritis trials is that there is no consensus on what the trial endpoints for efficacy should be. It is clear however that the goal for every lupus nephritis trial should be long-term preservation of kidney function. With this in mind we examined longitudinal lupus nephritis cohorts to look for short-term markers of long-term kidney survival. The goal was to find surrogate endpoints that could be used in trials of novel medications that could potentially be useful in deciding the effectiveness of an intervention in preserving renal function. In our first analysis of these data we looked at time to onset of new chronic kidney disease in lupus nephritis patients and determined that 12 months after initiation of treatment, the combination of the amount of protein in the patient’s urine, the serum creatinine concentration, and the change in kidney function from trial entry to 12 months predicted survival of the kidneys without developing chronic kidney disease. Based on that analysis, we propose a 12-month endpoint based on these variables for use in future clinical trials to determine whether a new intervention prevents onset of chronic kidney disease in lupus nephritis patients better than standard-of-care therapies.

SA-PO1100 Grazoprevir (GZR)/Elbasvir (EBR) Treatment of Hepatitis C Virus (HCV) Infection in Patients with Chronic Kidney Disease Stage 4/5: Final Results of the C-SURFER Phase 3 Study — David Roth, Annette Bruchfeld, Paul Martin, David R. Nelson, Marcelo Silva, Howard Monsour, Laurent Alric, Shuyan Wan, Beth Jackson, Bach-Yen Nguyen, Janice Wahl, Eliav Barr, Wayne L. Greaves. Miami, FL.

Although there have been tremendous strides in HCV treatment, patients with hepatitis C and advanced kidney disease have been underserved by current direct-acting antiviral hepatitis C treatment regimens. This study is good news for these patients and their doctors who have long waited for drugs that are less toxic and more potent than the standard treatment with ribavirin and weekly injections of interferon.

The C-SURFER study is the first phase 3 study to assess an all-oral treatment regimen for patients with HCV genotype 1 infection and advanced (stage 4–5) chronic kidney disease. 224 patients were randomly chosen to receive, once daily, grazoprevir plus elbasvir (n=122) or placebo drug (n=113) for 12 weeks. Most of the patients were on hemodialysis and many had other medical conditions e.g. diabetes, hypertension and cardiovascular disease. Treatment with grazoprevir plus elbasvir achieved a 99% response, with one relapse 12 weeks after the end of treatment. The high rate of response was seen across a wide range of patient types who participated in the study. The most common adverse events reported were headache, nausea, and fatigue, occurring at similar frequencies in patients receiving active and placebo drugs.

SA-PO1104 Impact of Vitamin D Supplementation on Endothelial and Vascular Function in Patients with Chronic Kidney Disease: A Randomized, Double-Blind, Placebo-Controlled Trial — Vivek Kumar, Ashok Kumar Yadav, Vinod Sharma, Manphool Singhal, Anupam Lal, Debasish Banerjee, Vivekanand Jha. Chandigarh, India.

In a study presented at the late breaking trials session of the Annual Meeting of the American Society of Nephrology, researchers from the Postgraduate Institute of Medical Education and Research, Chandigarh and George Institute for Global Health, New Delhi, India, found that nutritional vitamin D supplementation improved vascular function and reduced inflammation in patients with early stage of chronic kidney disease. In a randomised controlled trial, under direct supervision they gave two doses of 300,000 units of vitamin D to one group of patients 8 weeks apart whereas the patients in the other group received matching placebo. Several parameters of vascular function and biomarkers to measure status of inflammatory and immune activation were studied at baseline and after 16 weeks. Vitamin D levels increased in patients in the active treatment group whereas there was no change in the control arm. About 70% of patients receiving vitamin D demonstrated significant improvement in their vascular functions and improvement in biomarkers indicating reduction in the level of inflammatory and immune activation. In the pacebo arm only 5% patients showed improved vascular function and there was no change in the inflammatory and immune markers. Neither the patients nor the study doctors were aware of which patients received which treatment till the end.

'Vitamin D deficiency is common in patients with chronic kidney disease. Our study shows that simply identifying and correcting this abnormality has the potential to improve the outcomes in these patients' - said Dr Vivek Kumar, the first author of the study. 'About one in 10 people suffer from chronic kidney disease around the world. Most of these patients are destined to develop premature cardiovascular disease, hence mitigation of this risk is an important therapeutic goal' - pointed out Professor Vivekanand Jha, the leader of the group that did the study. 'Vitamin D is cheap and widely available, and through its favorable effects on inflammatory and immune functions, has the potential to favorably influence the course of these patients. This study has shown improvement in a range of parameters in vitamin-D treated patients. What makes this finding of special importance is that patients in both groups were already on optimal treatment to reduce cardiovascular risk, hence the benefit of vitamin D was additive', - he went on to say. This encouraging finding lays the foundation of doing trials to show whether this short-term benefit leads to improvement in clinically important end-points in long term studies.

SA-PO1105 Effect of Cholecalciferol vs. Calcitriol on Vascular Endothelial Function in CKD: A Randomized Active-Controlled Trial — Jessica B. Kendrick, Gerard John Smits, Emily Decker, Heather Farmer, Michel Chonchol. Denver, CO.

Cardiovascular disease is the leading cause of death in patients with chronic kidney disease. Arterial damage occurs early in the course of kidney disease and is a major factor that contributes to death in these patients. Vitamin D deficiency has been linked to increased vascular damage and cardiovascular disease. We conducted a randomized trial to determine if supplementation with nutritional or active vitamin D improves arterial function in patients with kidney disease. For the study, 128 patients with moderate to severe kidney disease and low blood levels of vitamin D were randomly assigned to nutritional (cholecalciferol) or active (calcitriol) vitamin D for 6 months. Blood vessel function was the main outcome of the study and was assessed by ultrasonography at the beginning and end of the study. Blood markers of mineral bone disease and inflammation were also measured at the beginning and end of study. One hundred and fifteen patients completed the study. After 6 months of treatment with nutritional or active vitamin D, there was no improvement in blood vessel function or a reduction in inflammation. Levels of parathyroid hormone decreased significantly in the active vitamin D group compared to the nutritional vitamin D group. Episodes of hypercalcemia were more frequent in the active vitamin D group compared to the nutritional vitamin D group. In conclusion, 6-month therapy with nutritional or active vitamin D did not improve arterial function or reduce inflammation in patients with chronic kidney disease.

SA-PO1107 Vascular Function and Uric Acid Lowering via Allopurinol in Stage III CKD: Results of a Double-Blinded Randomized Placebo-Controlled Study — Diana I. Jalal, Emily Decker, Loni J. Perrenoud, Nina Bispham, Tapan Mehta, Gerard John Smits, Richard J. Johnson. Aurora, CO.

Uric acid is a metabolic byproduct that is eliminated to a large extent by the kidney. In subjects with chronic kidney disease, uric acid levels are commonly elevated. While this may simply reflect retention of uric acid due to a reduction in kidney function, some studies have also linked uric acid to heart disease in subjects with kidney disease. Here we hypothesized that subjects with hyperuricemia and CKD (CKD) would show improvement in vascular function if the uric acid is lowered with a xanthine oxidase inhibitor (allopurinol). We conducted a clinical trial at the University of Colorado Anschutz Medical Center in which 80 patients with stage III CKD were randomly assigned to receive either placebo or allopurinol for 12 weeks. We evaluated the function of the blood vessels as their ability to dilate on their own or in response to a medication (nitroglycerin) before and after therapy. In addition, we measured markers of inflammation in the blood and in the cells obtained from the lining of the blood vessels. We found that allopurinol lowered uric acid levels effectively in the group of people that received it compared to the group that received placebo. There was no difference in side effects between both groups indicating that using allopurinol in patients with chronic kidney disease is safe. However, we found no difference in the primary endpoint. Specifically, there was no difference in the ability of the blood vessels to dilate on their own between the group that took allopurinol and the group that took placebo. The ability of the vessels to dilate in response to nitroglycerin tended to improve in the allopurinol-treated group compared to placebo but did not reach statistical significance. We found no difference in inflammation in the blood or in the vessels. Our study included a large number of patients with diabetes mellitus (60%). When we analyzed this subgroup, we again found a trend towards better ability for the blood vessels to dilate in response to nitroglycerin in patients with diabetes mellitus treated with allopurinol compared to the placebo-treated subjects. The study is limited because of the small number of people with chronic kidney disease but without diabetes mellitus. It is also a short term study in which the main measurement for cardiovascular risk is vascular function. Longer duration studies should be planned to better understand if lowering uric acid in patients with chronic kidney disease will reduce hard outcomes of cardiovascular disease such as heart attacks and stroke.

SA-PO1108 Podocyturia Is an Earlier and Superior Predictor of Cardiovascular Outcomes Than Is Albuminuria — Assaad Antoine Eid, Robert Habib, Kamal F. Badr. Beirut, Lebanon.

Heart attacks and stroke are the most serious outcomes of decades-long silent injury and disease affecting the small and large vessels of the heart and the brain. The amount of albumin in a random urine sample (“albuminuria”) predicts the risk for future heart disease and stroke because it reflects vascular injury in the kidney, which mirrors vascular injury in the heart and the brain, but also leads to abnormally high amounts of albumin being “filtered” and appearing in the urine. Such injury in the kidney is invariably associated with loss in the urine of cells names “podocytes”, which are closely involved in urine formation. Since the kidney may “re-absorb” (remove from the urine) a significant amount of filtered albumin, we hypothesized that increased filtration of albumin (vascular injury) may be occurring actively for years before urinary albumin levels begin to rise. We examined if measuring urinary podocytes (“podocyturia”) can predict cardiovascular outcomes before albumin excretion rate (AER) increases.

Type II diabetic subjects (mean age: 46/60 men/women) with initially low (“normal”) (AER) and free of overt cardiovascular disease (CVD) were studied. AER and urine levels of podocyte-specific proteins (podocin and nephrin) mRNAs were measured at baseline (Visit 1), 3-4 years later (Visit 2) and at 7 years (Visit 3). Development of CVD (acute coronary syndrome, stroke, and/or peripheral vascular disease) was collected as outcome. Visit 1 AER terciles exhibited similar time to CVD (p=0.127), in contrast with step-wise and substantial increases in CVD events predicted by Visit 1 podocin and nephrin terciles. Considered as continuous factors, the covariate-adjusted hazard ratios (95% confidence intervals) [HR] were highest for podocin mRNA [HR=15.9 (6.1-41.8); p<0.001], intermediate for nephrin mRNA [HR=7.61 (3.75-15.5); p<0•001] and lowest for AER [HR=1.17 (1.01-1.36); p=0•041].

We believe we have uncovered a clinical biomarker profile which predicts the development of heart attacks and strokes much earlier (at least 3-4 years) and with substantially greater prediction power than our best currently utilized measurement, albuminuria, and that urinary podocin and nephrin mRNA, and possibly other podocyte-tagging biomarkers, will replace albumin excretion as the best predictors of systemic vascular injury, and the earliest indicators of the need for intervention.

SA-PO1112 Monitoring in Dialysis (MiD) Study: Exploring the Timeline and Etiology of Increased Arrhythmias in Hemodialysis (HD) Patients — Prabir Roy-Chaudhury, Don E. Williamson, James A. Tumlin, Vijay K. Kher, Vikranth Reddy, David M. Charytan, Suresh Chandra Tiwari, Saurabh Pokhariyal, Amber S. Podoll. Tucson, AZ.

The Monitoring in Dialysis clinical study was a multicenter, observational, prospective study conducted in the United States and India where 66 maintenance hemodialysis patients (three times per week) were implanted with a continuous loop recorder (Medtronic Reveal® XT or LINQ™). A continuous loop recorder is a small insertable device that continuously monitors heart rhythms and records them either automatically or when the patient triggers collection using a hand-held device. The aim of the study was to determine whether there were periods during the dialytic week associated with a higher incidence of significant arrhythmic events. Data from each dialysis session was collected through 6 months, including changes in dialysis prescription, blood pressure, dialysate and blood flow rates, session duration, dry weight targets and ultrafiltration goals. In addition, pre and post-session blood chemistries were collected bi-weekly for 4 weeks and weekly for the remaining 22 weeks.

The primary objective of the study was to estimate the proportion of hemodialysis patients experiencing a clinically significant arrhythmia (CSA) over the 6-month follow-up period. CSA were defined as bradycardia ≤40 bpm for ≥6 sec, asystole ≥3 sec, sustained ventricular tachycardia ≥130 bpm for ≥30 sec and symptomatic arrhythmias. All documented arrhythmias were also analyzed and referred to as reviewer-confirmed arrhythmias (RCA).

During the first six months, 67% of subjects experienced a CSA, while 97% had at least one RCA. The highest rate of CSA occurred during the first dialysis session of the week (following the long interdialytic window). The rates of CSA decreased throughout the week; however, notably, the second highest rate of CSA occurred in the 12 hours prior to the first dialysis session in the week. The analysis also identified that a high pre-dialysis session potassium level is a predictor for increased arrhythmias. The highest risk of arrhythmias occur in patients with a significant change in potassium (pre session compared to post) and substantial volume removal during the session. These data suggest for the first time that relatively simple interventions such as optimizing the dialysis prescription may be employed to reduce the arrhythmic burden and lessen the rates of sudden cardiac death, which accounts for 20-30% of deaths in hemodialysis patients.

SA-PO1116 A Trial Assessing Use of a Wearable Artificial Kidney (WAK) in Patients Undergoing Maintenance Hemodialysis — Victor Gura, Matthew B. Rivara, Raj P. Munshi, Scott D. Bieber, Masoud Beizai, Carlos J. Ezon, Larry Kessler, Jonathan Himmelfarb. Beverly Hills, CA.

“We are pleased to present the results of our FDA-approved U.S. trial on seven patients conducted at the University of Washington at Seattle,” said UCLA/Cedars Sinai Nephrologist Victor Gura, MD, inventor of the Wearable Artificial Kidney (WAK). “The data provides proof of concept that the WAK is an effective and safe dialysis device that will greatly improve quality of life for ESRD patients. The results suggest that the WAK has the potential to reduce patient mortality and cut the exorbitant cost of treating kidney failure.” The epidemics of hypertension, diabetes and obesity have resulted in more than 600K patients in the U.S. and 2M worldwide who suffer from kidney failure requiring dialysis, and the numbers continue to rise. Keeping dialysis patients alive is very costly yet their quality of life is extremely poor and their mortality rate much too high. Just 5% of those awaiting a kidney transplant will live to receive one. There is a clearly a need for a new way to treat this disease. The Wearable Artificial Kidney (WAK) is a miniaturized, battery-operated, belt-like device that removes excess salt, water and toxins that accumulate in the body when the kidneys fail. It allows patients to walk around, work, eat and drink whatever they desire while cleansing their blood at a natural rate with less medication.

SA-PO1120 The Effects of Normal Saline and an Acetate-Buffered Crystalloid Solution on Hyperkalemia in Deceased Donor Renal Transplantation: A Randomized Blinded Trial — Laura Elisabeth Harris, Peter F. Mount, Francesco L. Ierino, David A. Story, Glenn M. Eastwood, Larry McNicol, Rinaldo Bellomo, Laurence Weinberg. Heidelberg, Australia.

Patients who receive a kidney transplant from a deceased donor are at risk in the post-operative period from the effects of high levels of potassium in the blood (hyperkalemia). Hyperkalemia may require urgent treatments, including dialysis, in order to prevent life-threatening heart rhythm disturbances. Kidney transplant patients routinely receive intravenous fluids during the transplant surgery and in the postoperative period. These fluids are given to help maintain enough blood flow to the kidney. Normal saline is the most commonly used intravenous fluid in kidney transplantation, largely because it does not contain potassium, and as a result it might cause fewer problems with hyperkalemia. A potential problem with saline, however, is that it contains a large quantity of chloride and some studies have found that the high chloride content of normal saline increases acid levels in the blood (acidemia), and that this in turn can cause or exacerbate hyperkalemia. Some studies in living donor kidney transplant recipients have found that using buffered crystalloid solutions, which have a lower chloride content, cause less acidemia and possibly lower potassium levels when compared to normal saline. This study was performed by the kidney transplant and anesthesiology teams at Austin Health, a university hospital in Melbourne, Australia. Forty-nine patients were randomized to receive either 0.9% normal saline (NS, 25 patients) or an acetate buffered crystalloid solution (Plasmalyte-148) (PL, 24 patients) both during the surgery and for 48-hours post-operatively. The main finding of the study was that the incidence of hyperkalemia in the first 48 hours postoperatively was statistically higher in the NS group (20/25 patients - 80%) than in the PL group (12/24 patients - 50%). In addition, patients in the NS group had higher levels of chloride and were more acidemic. There were, however, no differences between the groups in kidney function or hospital length of stay. The authors of the study conclude that this study supports the use of acetate buffered crystalloid solutions in preference to 0.9% normal saline for perioperative intravenous fluid management in patients undergoing deceased donor renal transplantation.

SA-PO1123 Impact of De Novo Donor Specific Antibodies on Graft Outcomes in Kidney Transplant Recipients Following Early Switch From Calcineurin Inhibitor to Everolimus: Analysis of the ELEVATE Trial — Johan W. De Fijter, Hallvard Holdaas, Patricia M. Lopez, Peter Bernhardt, Zailong Wang, Frans Claas, Wolfgang Arns, Josep M. Cruzado, Markus van der Giet. Leiden, Netherlands.

Transplant centers have recently started to introduce sophisticated new tests that identify whether transplant patients have developed antibodies which react specifically to the donated organ. These 'donor-specific antibodies' (DSA) dramatically increase the risk of hard-to-treat antibody-mediated rejection and the likelihood that the graft will fail. It is therefore imperative that immunosuppressive drugs given to prevent rejection do not increase the risk of developing DSA.

The large international randomized ELEVATE trial assessed outcomes in patients switched at three months after kidney transplantation from conventional anti-rejection treatment with a calcineurin inhibitor to everolimus, a mammalian target of rapamycin inhibitor. All patients also received mycophenolic acid. In this two-year study, the primary endpoint was the change in kidney function from the point of randomization to one year after transplantation, as assessed by estimated glomerular filtration rate (eGFR). This endpoint was not met: the mean difference in eGFR between the everolimus group and the patients who stayed on calcineurin inhibitor treatment was 1.7 mL/min/1.73m2 (p=0.134). By month 24, the mean value for eGFR was 62.5 mL/min/1.73m2 in the everolimus group and 57.4 mL/min/1.73m2 in the calcineurin inhibitor group (p=0.006).

The study also tested whether the development of DSA was affected by everolimus therapy. After the patients had been followed for two years post-transplantation, there was a low overall incidence of DSA which was balanced between the patients switched to everolimus and those who continued to receive a calcineurin inhibitor. There was no significant difference in the risk for any type of newly-formed DSA between the two groups.

SA-PO1124 Donor-Derived Cell-Free DNA in Plasma Increases with Rejection and Decreases after Treatment in Kidney Transplant Recipients — Marica Grskovic, Brian Christie, David Hiller, Robert Woodward, Jim Yee, Flavio Vincenti. Brisbane, CA.

Organ transplant patients require lifelong immunosuppression that necessitates a finely tuned therapeutic strategy. Sub-optimal dosing and the threat of allograft rejection must be balanced with excessive dosing and increased risks of infections and cancer. A significant unmet medical need exists for clinical diagnostic tools to permit surveillance management of transplant patients and improve the long-term outcomes of immunosuppressive therapy. One of the procedures used to monitor organ health is biopsy, which is invasive, time consuming, costly and risky.

Plasma cell-free DNA (cfDNA) has been described as a biomarker for prenatal testing, cancer, and organ transplantation, each of which present different clinical and technological challenges. There is limited clinical experience using cfDNA as a biomarker in kidney transplant recipients. In this new study, we collected plasma samples that were matched with tissue biopsies from kidney transplant recipients. The biopsy samples were classified as rejection or as quiescent (no rejection). The level of cfDNA derived from the transplanted organ (donor-derived or dd-cfDNA) was determined using a novel clinical-grade Next Generation Sequencing assay that does not require prior genotyping of donor or recipient. The level of dd-cfDNA was found to be higher in patients with biopsy-confirmed rejection and decreased following rejection treatment and recovery. In comparison, levels of serum creatinine, the commonly used biomarker of kidney function, were indistinguishable between the rejection and quiescent patients that underwent biopsy.

These results show promise in using cfDNA not only to detect rejection but also to monitor response to treatment. The ongoing measurement of cfDNA may allow clinicians to better personalize care, fine-tune immunosupression and improve the outcomes of patients.

ASN Kidney Week 2015Saturday, November 7, 2015Late-Breaking Posters Exhibit Hall A Additional Posters Include:

SA- O1091 The Remote Ischemic Preconditioning in Cardiac Surgery Trial (Remote IMPACT) — Michael Walsh, Hamilton, ON, Canada.

SA-PO1093 Efficacy and Safety of Bosutinib in Autosomal Dominant Polycystic Kidney Disease: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study — Kazimierz Ciechanowski, Vladimir Tesar, York P. Pei, Irina Barash, Megan Shannon, Ruifeng Li, Jason Williams, Matteo Levisetti, Steven Arkin, Andreas L. Serra. Szczecin, Poland.

SA-PO1095 A Phase 2, Double-Blind, Randomized Study of Fresolimumab or Placebo in Patients with Steroid-Resistant Primary Focal Segmental Glomerulosclerosis — James A. Tumlin, Flavio Vincenti, Fernando C. Fervenza, Kirk N. Campbell, Montserrat M. Díaz Encarnación, Manuel Praga, Denyse Thornley-Brown, Francisco Veríssimo Veronese, Beverly Accomando, Sara Engstrand, Steven R. Ledbetter, Julie Lin, John F. Neylan. Chattanooga, TN.

SA-PO1096 Effects of Sustained-Release Beraprost Sodium in Patients with Primary Glomerular Disease or Nephrosclerosis: The CASSIOPEIR Study — Toshiro Fujita, Xueqing Yu, Suhnggwon Kim, Hidetomo Nakamoto, Hideki Origasa, Hajimu Kurumatani, Takashi Kiriyama. Tokyo, Japan. SA-PO1098 A Randomized Trial of Rituximab in Advanced IgA Nephropathy — Richard A. Lafayette, Pietro A. Canetta, Brad H. Rovin, Gerald B. Appel, Marie C. Hogan, Stephen B. Erickson, Fernando C. Fervenza. Stanford, CA.

SA-PO1101 Long-Term (52-Week) Efficacy and Safety of ZS-9 in the Treatment of Hyperkalemia: Interim Results from a Phase 3 Open-Label, Multi-Center, Multi-Dose Maintenance Study — James A. Tumlin, Mikhail Kosiborod, Pablo E. Pergola, Wajeh Y. Qunibi, David K. Packham, Simon D. Roger, Edgar V. Lerma, Steven Fishbane, Henrik S. Rasmussen, Bruce S. Spinowitz. Chattanooga, TN.

SA-PO1102 Interleukin-1 Inhibition and Vascular Function in Patients with Chronic Kidney Disease (CKD): A Randomized Controlled Trial — Kristen L. Nowak, Michel Chonchol, Talat Alp Ikizler, Heather Farmer, Natjalie Salas, Rafia I. Chaudhry, Wei Wang, Gerard John Smits, Adriana Hung. Aurora, CO.

SA-PO1106 Vitamin D Receptor Activation and Dietary Sodium Restriction to Reduce Residual Albuminuria in Chronic Kidney Disease — Martin H. De Borst, Charlotte A. Keyzer, Fenna van Breda, Marc G. Vervloet, Gozewijn Dirk Laverman, Marc H. Hemmelder, Wilbert M. Janssen, Hiddo Jan Lambers Heerspink, Stephan J.L. Bakker, Gerjan Navis. Groningen, Netherlands.

SA-PO1109 Empagliflozin Reduces Microalbuminuria and Macroalbuminuria in Patients with Type 2 Diabetes — David Cherney, Søren Søgaard Lund, Bruce A. Perkins, Per-Henrik Groop, Mark E. Cooper, Stefan Kaspers, Susanne Crowe, Hans-Jürgen Woerle, Maximilian von Eynatten. Toronto, ON, Canada.

SA-PO1110 Vadadustat, a Novel Oral Treatment for Anemia of Chronic Kidney Disease, Maintains Stable Hemoglobin Levels in Dialysis Patients Converting from Erythropoiesis-Stimulating Agents — Volker H. Haase, Charlotte S. Hartman, Bradley J. Maroni, Ramin Farzaneh-Far, Peter A. McCullough. Nashville, TN.

SA-PO1113 The Occurrence of Cardiac Arrhythmias in Hemodialysis Patients is Linked to the Hemodialysis Procedure and to Electrolyte Abnormalities as Recorded by Implantable Loop Recorders — Christian Combe, Antoine Benard, Hélène Savel, F. Sacher. Bordeaux, France.

SA-PO1115 Comparison of the Efficacy and Safety of Intravenous (IV) Etelcalcetide (AMG 416) and Oral Cinacalcet (CIN) in Patients on Hemodialysis (HD) with Secondary Hyperparathyroidism (sHPT) — Kevin J. Martin, Geoffrey A. Block, Sunfa Cheng, Bastian Dehmel, Reshma Kewalramani, David M. Spiegel, Hao Wang, Glenn Matthew Chertow. St Louis, MO.

SA-PO1117 CR845, a Novel Kappa Opioid Receptor Agonist Reduces Moderate-to-Severe Pruritus and Improves Quality of Life in Chronic Kidney Disease Patients Undergoing Hemodialysis — Robert Spencer, Vandana S. Mathur, James A. Tumlin, Joseph W. Stauffer, Frederique Menzaghi. Shelton, CT.

SA-PO1118 The ASSertID Study: Feasibility Randomised Controlled Trial of Drug Treatment for Depression in Patients on Haemodialysis — Ayman Guirguis, Michael K. Almond, Joseph Chilcot, Andrew Davenport, Clara Day, Naomi Fineberg, Karin Friedli, Benjamin Spencer, David Wellsted, Ken Farrington. Hatfield, Hertfordshire, United Kingdom.

SA-PO1119 Randomised Controlled Trial to Determine the Appropriate Time to Initiate Pertioneal Dialysis after Insertion of Catheter to Minimise Complications — Helen G. Healy, George T. John, Edward Yeoh, Nicola Williams, Thin M. Han, Lakshmanan Jeyaseelan, Kavitha Ramanathan, Dwarakanathan Ranganathan. Brisbane, Queensland, Australia.

SA-PO1120 The Effects of Normal Saline and an Acetate-Buffered Crystalloid Solution on Hyperkalemia in Deceased Donor Renal Transplantation: A Randomized Blinded Trial — Laura Elisabeth Harris, Peter F. Mount, Francesco L. Ierino, David A. Story, Glenn M. Eastwood, Larry McNicol, Rinaldo Bellomo, Laurence Weinberg. Heidelberg, Australia.

SA-PO1122 Eculizumab in Prevention of Acute Antibody-Mediated Rejection in Sensitized Deceased-Donor Kidney Transplant Recipients: Updated 12-Month Outcomes — D. Glotz, G. Russ, Lionel Rostaing, Christophe M. Legendre, Steven J. Chadban, J. Grinyo, Nizam Mamode, Gunnar Tufveson, Lionel Couzi, P. Riggoti, Y. Lebranchu, S. Sandrini, W. Marks. Paris, France.

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ASN Kidney Week 2015, the largest nephrology meeting of its kind, will provide a forum for more than 13,000 professionals to discuss the latest findings in kidney health research and engage in educational sessions related to advances in the care of patients with kidney and related disorders. Kidney Week 2015 will take place November 3–8, 2015, in San Diego, CA.The content of this article does not reflect the views or opinions of The American Society of Nephrology (ASN). Responsibility for the information and views expressed therein lies entirely with the author(s). ASN does not offer medical advice. All content in ASN publications is for informational purposes only, and is not intended to cover all possible uses, directions, precautions, drug interactions, or adverse effects. This content should not be used during a medical emergency or for the diagnosis or treatment of any medical condition. Please consult your doctor or other qualified health care provider if you have any questions about a medical condition, or before taking any drug, changing your diet or commencing or discontinuing any course of treatment. Do not ignore or delay obtaining professional medical advice because of information accessed through ASN. Call 911 or your doctor for all medical emergencies.Founded in 1966, and with nearly 16,000 members, the American Society of Nephrology (ASN) leads the fight against kidney disease by educating health professionals, sharing new knowledge, advancing research, and advocating the highest quality care for patients.